Inhibition of γ-secretase cleavage in the notch signaling pathway blocks HSV-2-induced type I and type II interferon production

We have evaluated the role of γ-secretase, which is a crucial component in the Notch-induced signaling cascade, on herpes simplex virus type 2 (HSV-2)-induced innate and acquired interferon responses in human CD4(+) T cells and plasmacytoid dendritic cells (pDC). We found that blockade of the Notch signaling pathway with a pharmacological γ-secretase inhibitor blocked both HSV-2-induced interferon-γ (IFN-γ) production in CD4(+) T cells, and HSV-2-induced IFN-α production in pDC in a dose-dependent fashion. These effects were not due to an overall suppressive capacity of the γ-secretase inhibitor, as it affected neither phytohemagglutinin (PHA)-induced IFN-γ production in CD4(+) T cells, nor CpG-induced IFN-α production in pDC. Our data suggest that Notch signaling could be involved in HSV-2-induced interferon responses in CD4(+) T-cells and pDC.     

MDA5 is SUMOylated by PIAS2β in the upregulation of type I interferon signaling

Retinoic acid-inducible protein I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are cytosolic viral RNA sensors that induce type I interferon production (IFN). In this study, we found that MDA5 undergoes inducible SUMOylation by small ubiquitin-like modifier-1 (SUMO-1) in response to polyI:C stimulation. Enhanced SUMOylation of MDA5 by exogenously expressed SUMO-conjugating enzyme Ubc9 correlated with upregulation of IFN expression and repressed virus replication. Conversely, overexpression of a SUMOylation-deficient mutant of Ubc9 or knockdown of endogenous Ubc9 reduced IFN production. Furthermore, we showed that PIAS2β, a SUMOylation E3 ligase, could specifically interact with and enhance the SUMOylation of MDA5. Consequently, PIAS2β knockdown reduced the SUMOylation of MDA5 and the IFN production. Collectively, these findings suggest that SUMO-1 modification of MDA5 possibly via PIAS2β may play a role in the MDA5-mediated IFN response to viral infections.     

Microarray analysis of gene expression in metastatic gastric cancer cells after incubation with the methylation inhibitor 5-aza-2′-deoxycytidine

While the exact mechanisms involved in cancer metastasis are not fully clarified, the altered expression of many different genes has been reported. Hypermethylation of the promoters of cancer-related genes is often associated with their inactivation during tumorigenesis and may also be involved in metastasis. Here we used cDNA microarrays to examine the different gene expression profiles of a primary gastric adenocarcinoma cell line RF1 and its derivative metastasis subline RF48. Compared with RF1, 49 genes were down-regulated and 8 genes were up-regulated in RF48. After treatment of RF48 cells with a DNA methylation inhibitor, 5-aza-2′-deoxycytidine, 101 genes were up-regulated and 1 gene was down-regulated in treated RF48 when compared with untreated RF48. Comparing gene expression patterns of untreated RF1, untreated RF48 and treated RF48 cells showed 5 genes expressed in RF1 but silenced in RF48, which were reactivated after 5-aza-2′-deoxycytidine treatment. Two of those 5 genes have CpG islands within their promoter regions, suggesting that those genes activated by 5-aza-2′-deoxycytidine may result from the direct inhibition of promoter methylation. In conclusion, using global gene expression analysis together with inhibition of DNA methylation, we demonstrate that hypermethylation of the promoters of certain cancer-related genes may play a role in cancer metastasis.     

Parathyroid hormone enhances calcium current in snail neurones — Simulation of the effect by phorbol esters

Effects of parathyroid hormone substance (PTH) on the voltage-activated calcium current (I _Ca) were studied on intracellularly perfused neurones of the snail, Helix pomatia, under voltage-clamp conditions. Application of 0.1 nM PTH produced a marked potentiation of the current. The effect developed slowly (60–70 min) and remained after removal of PTH. Potentiation could be observed in most neurones, but varied considerably from cell to cell; in some neurones I _Ca was increased 2- to 3-fold. Addition of ethylenebis(oxonitrilo)tetraacetate (EGTA, 10 mM) to, or removal of adenosine 5-triphosphate (ATP, 2 mM) from the intracellular perfusing solution resulted in a suppression or attenuation of the potentiating effect. The effect could be reproduced by the synthetic 1–34 amino acid fragment of PTH. Extracellularly applied protein kinase-C (PK-C) activator phorbol ester phorbol 12-myristate 13-acetate (PMA, 0.1–10 M) produced a similar slow increase in I _Ca (up to 1.5- to 2-fold), while its inactive analogue (4-phorbol ester) had no effect on I_Ca. The effects of PTH and PMA were not additive. PK-C inhibitors [1-(5-isoquinoline-sulphonyl)-2-methylpiperazine hydrochloride] (H-7, 100 M) and staurosporine (100 M) as well as calcium channel antagonists Cd²⁺, verapamil, nifedipine and nimodipine depressed the effect of PTH. The chloride channel blocker 4,4-diisothiocyanato-stilbene-2,2-disulphonic acid (DIDS, 1 mM) did not affect the potentiating action of PTH. Activation of the adelylate cyclase system also potentiated I _Ca in some neurones, but this effect had a different time course and was additive to the effect of PTH. A conclusion is made that activation of PK-C may mediate the slowly developing enhancement of I _Ca by PTH.     

Modulation of lipopolysaccharide-induced memory insult, γ-secretase,and neuroinflammation in triple transgenic mice by 5-lipoxygenase

Besides amyloid and tau pathology, a constant feature of Alzheimer's disease (AD) is an intense inflammatory response, which is considered an active player in its pathogenesis. The 5-Lipoxygenase (5LO) is a proinflammatory enzyme and an endogenous modulator of AD-like phenotype in mouse models of the disease. To further understand the role of 5LO in AD pathogenesis, we exposed the triple transgenic (3×Tg) and 3×Tg/5LO knockout mice to lipopolysaccharide (LPS), a known inducer of neuroinflammation, and evaluated its effect on their AD-like phenotype. 3×Tg mice treated with LPS manifested a worsening of behavior, γ-secretase up-regulation, and increased neuroinflammatory responses. These effects were completely prevented in 3×Tg mice genetically deficient for 5LO. By contrast, the absence of 5LO did not protect against increase in tau phosphorylation at specific epitopes that were mediated by the activation of the cyclin-dependent kinase 5. Our data demonstrate that the 5LO pathway affects key neuropathological features of the AD-like phenotype (behavior, abeta, microgliosis, astrocytosis) but not others (tau pathology) in the LPS-dependent neuroinflammation model. The opposite ways whereby 5LO influences the LPS-dependent effects in vivo supports the complex nature of the neuroinflammatory response in AD and its differential role in modulating amyloid and tau neuropathology.     

Down-regulating ribonuclease inhibitor enhances metastasis of bladder cancer cells through regulating epithelial–mesenchymal transition and ILK signaling pathway

Accumulating evidences implicate that ribonuclease inhibitor (RI) plays a suppressing role in cancer development. However, the mechanisms underlying antitumor of RI remain largely unknown. Epithelial–mesenchymal transition (EMT) is regarded as a key event in tumor progression. The reports have demonstrated that EMT was implicated in metastasis of bladder cancer. Therefore, we suppose that RI might involve regulating EMT of bladder cancer. Here bladder cancer T24 cells were transfected with pGensil-1-siRNA-RI vectors. HE staining, living cell observation, Phalloidine-FITC staining of microfilament, cell adhesion, scratch migration, and Matrigel invasion were examined respectively. RI expression and colocalization with ILK were detected using confocal microscope. Proteins associated with EMT were determined with Western blotting and immunohistochemistry in vivo and in vitro. Effects of RI expression on tumor growth, metastasis and EMT related proteins in BALB/C nude mouse and clinical human bladder cancer specimens were valued with histological, immunohistochemical and immunofluorescent examination respectively. We demonstrated that down-regulating RI increased cell proliferation, migration and invasion, changed cell morphology and adhesion, and rearranged cytoskeleton by inducing EMT and ILK signaling pathway in bladder cancer cells. In addition, we showed that down-regulating RI promoted tumorigenesis and metastasis of bladder cancer in vivo. Finally, we found that bladder cancer with invasive capability had higher Vimentin, Snail, Slug and Twist as well as lower E-cadherin and RI expression in clinical human specimens. Our results suggest that RI could play a novel role in inhibiting metastasis of bladder through regulating EMT and ILK signaling pathway.     

Regulation of SHP2 by PTEN/AKT/GSK-3β signaling facilitates IFN-γ resistance in hyperproliferating gastric cancer

Oncogenic activation accompanied by escape from immune surveillance, such as IFN-γ resistance, is critical for cancer cell growth and survival. In this study, we investigated the crosstalk signaling between IFN-γ resistance and signaling of hyperproliferation in gastric cancer cells. IFN-γ inhibited the cell growth of MKN45 cells but not hyperproliferating AGS cells. AGS cells did not respond to IFN-γ because of a decrease in STAT1 but not due to dysfunctional IFN-γ receptors. Signaling of PI3K/AKT, as well as MEK/ERK, was required for the hyperproliferation; notably, PI3K/AKT alone mediated the IFN-γ resistance. Aberrant Src homology-2 domain-containing phosphatase (SHP) 2 determined IFN-γ resistance but unexpectedly had no effects on hyperproliferation or ERK activation. In the IFN-γ resistant cells, inactivation of glycogen synthase kinase (GSK)-3β by PI3K/AKT was important for SHP2 activation but not for hyperproliferation. An imbalance of AKT/GSK-3β/SHP2 caused by a reduction of PTEN was important for the crosstalk between IFN-γ resistance and hyperproliferation. PI3K is constitutively expressed in AGS cells and immunohistochemical staining showed a correlation between hyperproliferation and expression of SHP2 and STAT1 in gastric tumors. These results demonstrate the effects of PTEN/AKT/GSK-3β/SHP2 signaling on IFN-γ resistance in hyperproliferating gastric cancer cells.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.     

The effect of Fufangkushen on gastric cancer cell killing by lines SGC-7901 human γδT cell

Objective To explore the effect of Fufangkushen on gastric cancer cell killing by human γδT cells. Methods Isopentenyl pyrophosphate method was used to amplify human peripheral blood γδT cells in vitro. Fufangkushen at various concentrations was used to induce γδT cells and gastric cancer cell lines SGC-7901 for 24 hours, MTr assays was used to detect inhibitory effect of Fufangkushen on these cell lines, LDH assays was used to measure the cytotoxic activity of γδT cells, and flow cytometry was used to detect apoptosis of γδT cells and SGC-7901 before and after the treatment. Results Ten days after cultivation, proliferation ra-tio of γδT cells increased from 4.21% to 70.35% and CD44 was up to 94.0%. Inhibitory rate of Fufangkush-en on SGC-7901 at various concentrations was significantly higher than that on γδT cells (22.3% vs-22.4%, P<0.05). The negative inhibitory ratio on γδT cells showed a dose-dependent manner with Fufangkushen's concentrations ranging from 1/5 to 1/400. γδT cells cytotoxic activity to SGC-7901 induced by Fufangkushen for 24 h was higher than control group, (83.6% vs 71.2%, P<0.05). Apoptotic rate was significantly lower in γδT cells than in SGC-7901 (4.64% vs49.23%, P<0.05). Conclusion Fufangkushen, within routine concentration ranges, can promote γδT cells' proliferation, inhibit tumor cell growth and enhance γδT cells' cytotoxic activity. This may be beneficial to tumor adoptive immunotherapy and provide evidence for the appli-cation of Fufangkushen in the treatment of tumors.     

Bortezomib enhances the radiosensitivity of hypoxic cervical cancer cells by inhibiting HIF-1α expression

Objective: This study aimed to investigate the radiosensitivity of bortezomib to cervical cancer and the possible underlying mechanism. Methods: HeLa and SiHa cell lines with or without hypoxia treatment were divided into control, radiation alone, bortezomib alone, and radiotherapy plus bortezomib groups. CCK8 assay, clone formation assay, flow cytometry, and immunofluorescence test were used to measure cell proliferation, colony formation, apoptosis, and DNA double-strand break (DSB). Western blot analysis was performed to detect the expression of HIF-1α, PARP-1, and caspase-3, -8, and -9. Result: Statistical analysis of data revealed that bortezomib at nanomolar level exerted a radiosensitization effect on both cervical cancer cell lines in normoxia or hypoxia. Western blot analysis showed that the drug could inhibit hypoxia-related HIF-1α expression to increase apoptosis-related caspase-3, -8, and -9 activation and DNA DSB-related PARP-1 cleavage. Conclusions: Radiotherapy sensitization of bortezomib on cervical cancer cell lines had a drug-dose relation, and sensitization in hypoxia was more remarkable than in normoxia. Bortezomib may be a potential radiotherapy sensitization drug for cervical cancer.     

Expression of Krűppel-like factor 5 in gastric cancer and its clinical correlation in Taiwan

Krűppel-like factors (KLFs), highly conserved zinc-finger proteins, play either anti- or pro-proliferation roles in different human cancers through regulating a wide range of genes’ expression. Here, we investigated the expression of KLF5 in gastric cancers and its correlation with clinicopathological parameters and overall survival rates. In this study, KLF5 expression was measured by an immunohistochemical microarray assay of tissue taken from 76 surgical specimens. Higher KLF5 expression was significantly associated with lower tumor grade (P < 0.001). Nuclear staining of the KLF5 expression was significantly associated with a higher tumor grade (P = 0.000), higher clinical stage (P = 0.019), lymph node status (P = 0.016), and 2-year survival (P = 0.017). Patients with nuclear staining of KLF5 had a significantly lower disease-free survival rate compared to patients with negative nuclear staining, as defined by a log-rank test (P = 0.041). Our results revealed that KLF5 may play an oncogenetic role in gastric carcinogenesis.