Apoptosis in human hepatoma cell line SMMC-7721 induced by water-soluble macromolecular components of Artemisia capillaris Thunberg.

The aim of this study was to investigate the effect of water-soluble macromolecular components of Artemisia capillaris Thunberg (ACT) on human hepatoma cell line SMMC-7721 (SMMC-7721). The morphological changes of SMMC-7721 were observed under a light microscope and an electron microscope. Inhibition of proliferation was measured with a colorimetric MTT assay. It was discovered that ACT extract-treated cells exhibit morphological changes typical of apoptosis, including condensed chromatin and a reduction in volume. ACT extract at 25-200 microg/ml dose-dependently inhibited the proliferation of SMMC-7721. The 50% effective dose, evaluated on day 3 of exposure to the extract, was 64.52+/-3.53 microg/ml. Upon gel electrophoresis, the fragmented DNA showed a characteristic ladder pattern. Cell cycle analyses revealed that ACT induced cell cycle arrest at the G0/G1 phase.     

Simaomicin α, a polycyclic xanthone, induces G1 arrest with suppression of retinoblastoma protein phosphorylation

Recent progress in cancer biology research has shown that abnormal proliferation in tumor cells can be attributed to aberrations in cell cycle regulation, especially in G₁ phase. During the course of searching for microbial metabolites that affect cell cycle distribution, we have found that simaomicin α, a polycyclic xanthone antibiotic, arrests the cell cycle at G₁ phase. Treatment of T-cell leukemia Jurkat cells with 3 nM simaomicin α induced an increase in the number of cells in G₁ and a decrease in those in G₂–M phase. Cell cycle aberrations induced by simaomicin α were also detected in colon adenocarcinoma HCT15 cells. Simaomicin α had antiproliferative activities in various tumor cell lines with 50% inhibitory concentration values in the range of 0.3–19 nM. Furthermore, simaomicin α induced an increase in cellular caspase-3 activity and DNA fragmentation, indicating that simaomicin α promotes apoptosis. The retinoblastoma protein phosphorylation status of simaomicin α-treated cell lysate was lower than that of control cells, suggesting that the target molecule of simaomicin α is in a pathway upstream of retinoblastoma protein phosphorylation. In the course of evaluating polycyclic xanthone antibiotics structurally related to simaomicin α, we also found that cervinomycin A1 stimulated accumulation of treated cells in G₁ phase. These results indicate that the polycyclic xanthones, including simaomicin α and cervinomycin A1, may be candidate cancer chemotherapeutic agents. ( Cancer Sci 2009; 100: 322–326)     

白眉蝮蛇去整合素rAdinbitor对人肝癌细胞系SMMC-7721细胞黏附与增殖的抑制作用

Objective:To investigate the effects of rAdinbitor on the adhesion and proliferation of human hepatoma cell strain SMMC-7721.Methods:Cell adhesion assay was used to observe the effect of rAdinbitor on the adhesion of SMMC-7721 cells to fibronectin (FN).Crystal violet staining was performed to detect the influence of rAdinbitor on the adhesion of SMMC7721 cells.MTT assay was employed to detect the inhibitory effects of different concentration of rAdinbitor on the proliferation of SMMC-7721 cells.The morphologic changes of the control SMMC-7721 cells and the apoptotic cells induced by 200 μg/mL rAdinbitor for 36 h were observed under light microscope after HE staining.Flow cytometry analysis was applied to determine the apoptosis rate of SMMC-7721 cells.Results:(1) FN promoted the adhesion of human hepatoma cell strain SMMC-7721 in a dose-dependent manner.(2) rAdinbitor could dose-dependently inhibit the adhesion of SMMC-7721 cells to FN.The higher the concentration was,the stronger the inhibition was.There was significant difference among the groups (P＜0.05).(3) rAdinbitor had a strong inhibition on the proliferation of SMMC-7721 cells and showed a dose-dependent manner (P＜0.05).After a 48 h exposure,the IC5o value of rAdinbitor was 177.83 μg/mL.(4) After exposure of SMMC-7721 cells to 200 μg/mL rAdinbitor for 36 h,the eady morphologic changes appeared and the apoptosis rate was 20.68%,significantly higher than that of the control group (2.38%,P＜0.05).Conclusion:rAdinbitor can dose-dependently inhibit the SMMC-7721 cells adhesion to FN,and can inhibit the proliferation in dose-dependent manner and promote their apoptosis.     

水飞蓟宾对人肝癌细胞SMMC-7721体外增殖的影响

目的:探讨水飞蓟宾对SMMC-7721细胞的抗增殖作用。方法:MTT法观察对细胞的抑制作用;免疫细胞化学法检测增殖细胞核抗原(PCNA)及Ki-67的表达;流式细胞仪分析细胞周期及凋亡;光镜及透射电镜观察细胞形态学的变化。结果:水飞蓟宾可抑制SMMC-7721的增殖,并降低PCNA、Ki-67的表达及引起细胞G2/M期阻滞,同时诱导凋亡。光镜发现细胞体积缩小,核固缩深染;电镜可见凋亡及凋亡小体。结论:在体外,水飞蓟宾可抑制SMMC-7721细胞的增殖。     

Flow Cytometric Bromodeoxyuridine/DNA Analysis of Hyperthermia and/or Adriamycin for Human Pancreatic Adenocarcinoma Cell Line Capan-2

The effects of hyperthermia, adriamycin (ADM), and hyperthermia combined with ADM on pancreatic cancer cells were investigated from the viewpoint of cytokinetics using flow cytometric bromodeoxyuridine (BrdUrd)/DNA analysis. Human pancreatic adenocarcinoma cell line Capan-2 was used. The untreated cells could be clearly divided into G₁, S, G₂M phases on contour plots of BrdUrd/DNA distribution. After heat treatment at 41–43°C, there was an accumulation of cells in the G₂M phase which was correlated with the increase in temperature. After heat treatment at 44 or 45°C, there was marked increase in non BrdUrd-labeled cells in the S phase. ADM caused no change in the percent of non BrdUrd-labeled cells in the S phase, even after treatment with a concentration of 1.0 μg/ml, though that concentration of ADM caused a marked increase in the percent of cells in the G₂M phase. After hyperthermia combined with ADM, the accumulation of the G₂M phase increased remarkably, and was significantly higher than that after each treatment alone ( P < 0.005); however, non BrdUrd-labeled cells in the S phase did not increase. In this study the synergistic effect of hyperthermia combined with ADM in increasing the percent of cells in the G₂M phase could be observed by flow cytometry. The study illustrates the importance of performing in vitro flow cytometric BrdUrd/DNA analysis of combined therapy prior to the use of the combined therapy in patients.     

Chinese Medicinal Herb, Acanthopanax gracilistylus, Extract Induces Cell Cycle Arrest of Human Tumor Cells in vitro

We investigated the effect of a Chinese medicinal herb, Acanthopanax gracilistylus (AG), extract (E) on the growth of human tumor cell lines in vitro. AGE markedly inhibited the proliferation of several tumor cell lines such as MT-2, Raji, HL-60, TMK-1 and HSC-2. The activity was associated with a protein of 60 kDa, which was purified by gel-filtration chromatography. Cell viability analyses indicated that the treatment with AGE inhibits cell proliferation, but does not induce cell death. The mechanism of AGE-induced inhibition of tumor cell growth involves arrest of the cell cycle at the G₀/G₁ Stage without a direct cytotoxic effect. The cell cycle arrest induced by AGE was accompanied by a decrease of phosphorylated retinoblastoma (Rb) protein. Furthermore, cyclin-dependent kinases 2 and 4 (Cdk2 and Cdk4), which are involved in the phosphorylation of Rb, were also decreased. These results suggest that AGE inhibits tumor cell growth by affecting phosphorylated Rb proteins and Cdks.     

Skp2在三氧化二砷诱导的肝癌SMMC-7721细胞周期阻滞中的表达变化和意义

目的: 探讨三氧化二砷(As₂O₃)对肝癌SMMC-7721细胞周期的影响,及其与细胞周期素依赖性激酶抑制因子(CDKI)p27^kip1和p27^kip1相关蛋白S期激酶相关蛋白2(S-phase kinase-associated protein2,Skp2)的关系,为临床应用提供依据。 方法: 体外培养人肝癌细胞株SMMC-7721,用2μmol/LAs₂O₃处理72h,流式细胞仪检测细胞周期变化,采用核浆分离、Western Blot技术及细胞免疫荧光技术检测该过程中p27^kip1、Skp2在SMMC-7721细胞中的表达变化及亚细胞定位情况。 结果: 与对照组比较,As₂O₃使SMMC-7721细胞周期阻滞在G₂/M期。经As₂O₃作用的人肝癌细胞p27^kip1蛋白水平增加,Skp2蛋白水平降低,同时27^kip1发生从胞浆到胞核的易位。 结论: As₂O₃可下调Skp2的表达,从而促进SMMC-7721细胞中p27^kip1的积聚,干扰细胞周期的进程,抑制SMMC-7721细胞的增殖。     

沙利度胺对人肝癌细胞株SMMC-7721体外生长的抑制作用

目的 研究沙利度胺对人肝癌细胞株SMMC-7721体外生长的抑制作用及其可能的机制.方法 将不同浓度的沙利度胺作用于人肝癌细胞株SMMC-7721,采用四甲摹偶氮唑蓝(MTT)法检测沙利度胺对SMMC-7721细胞的增殖抑制作用.将SMMC-7721细胞培养至对数生长期,采用DNA琼脂糖凝胶电泳、荧光显微镜观察、流式细胞仪检测等方法 观察沙利度胺处理后SMMC-7721细胞的凋亡梯度、形态学变化和凋亡率,并对凋亡调控蛋白caspase-3的表达进行测定.采用酶联免疫吸附(ELISA)法测定不同浓度的沙利度胺处理后SMMC-7721细胞表达血管内皮生长因子(VEGF)的变化.结果 沙利度胺的浓度从3.125μg/ml增至200μg/ml时,其对SMMC-7721细胞的增殖抑制率从11.7%增至34.2%;当沙利度胺的浓度>25 μg/ml时,其对SMMC-7721细胞的增殖抑制作用明显强于空白对照组(P<0.05).200 μg/ml的沙利度胺处理SMMC-7721细胞24 h后,行琼脂糖凝胶电泳,可见到DNA梯形条带;48 h后梯形条带更明显,并且在荧光显微镜下可见SMMC-7721细胞出现核固缩和核裂解现象.200μg/ml的沙利度胺处理SMMC-7721细胞12、24、48和72 h时,碘化丙啶(PI)法检测SMMC-7721细胞的凋亡率分别为3.1%±0.5%、8.4%±1.3%、19.4%±3.5%和25.8%±2.1%,24 h起的凋亡率均明显高于空白对照组SMMC-7721细胞48 h的自然凋亡率(1.6%±0.6%,均P<0.05).50、100和200μg/ml的沙利度胺处理SMMC-7721细胞48 h时,Annexin V-FITC/PI双标法检测SMMC-7721细胞的凋亡率分别为8.7%±1.2%、16.8%±2.5%和25.4%±4.5%,均明显高于空白对照组SMMC-7721细胞48 h的自然凋亡率(2.1%±0.5%,均P<0.05).随着沙利度胺浓度的增加,表达caspase-3蛋白的SMMC-7721细胞数量不断增加,而SMMC-7721细胞中VEGF的含量却逐渐下降.结论 沙利度胺可能通过诱导肝癌细胞的凋亡、抑制肿瘤血管的生成而发挥双重抗肿瘤生长的作用.     

顺铂对肝癌细胞株SMMC-7721中SATB1表达的影响

目的:探讨肝癌细胞株SMMC-7721加入顺铂后细胞形态及特异AT序列结合蛋白1(special AT-rich sequence-bindingprotein 1,SATB1)表达的变化。方法:SMMC-7721细胞株中加入不同浓度(0、2.5、5和10μg/ml)顺铂培养24 h后,在倒置显微镜下观察细胞形态变化,半定量逆转录RT-PCR法检测SATB1 mRNA的表达,Western blot检测SATB1蛋白的表达。结果:SMMC-7721细胞与不同浓度顺铂共培养24 h后,倒置显微镜下可见细胞形态明显改变,细胞数减少,损伤、死亡的细胞增多。SATB1mRNA及蛋白的表达均随着顺铂浓度的增加而减少,其中5和10μg/ml顺铂组与对照组间的差异均有统计学意义(P<0.05或P<0.01)。结论:顺铂可抑制SMMC-7721细胞增殖及SATB1的表达,从而达到抑制肝癌细胞生长的目的。     

Mechanisms of Growth Inhibition of Human Lung Cancer Cell Line, PC-9, by Tea Polyphenols

(–)-Epigallocatechin gallate (EGCG), the main constituent of green tea, and green tea extract show growth inhibition of various cancer cell lines, such as lung, mammary, and stomach. We studied how tea polyphenols induce growth inhibition of cancer cells. Since green tea extract contains various tea polyphenols, such as EGCG, (–)-epigallocatechin (EGC), (–)-epicatechin gallate (ECG), and (–)-epicatechin (EC), the inhibitory potential of each tea polyphenol on the growth of a human lung cancer cell line, PC-9 cells, was first examined. EGC and ECG inhibited the growth of PC-9 cells as potently as did EGCG, but EC did not show significant growth inhibition. The mechanism of growth inhibition by EGCG was studied in relation to cell cycle regulation. Flow cytometric analysis revealed that treatment with 50 μM and 100 μM EGCG increased the percentages of cells in the G₂-M phase from 13.8% to 15.6% and 24.1%, respectively. The DNA histogram after treatment with 100 μM EGCG was similar to that after treatment with genistein, suggesting that EGCG induces G₂-M arrest in PC-9 cells. Moreover, we found by microautoradiography that [³H]EGCG was incorporated into the cytosol, as well as the nuclei. These results provide new insights into the mechanisms of action of EGCG and green tea extract as cancer-preventive agents in humans.     

菱角提取物诱导人肝癌SMMC-7721细胞凋亡

[目的]探讨菱角提取物对人肝癌SMMC-7721细胞的增殖抑制及诱导凋亡作用。[方法]采用MTT法检测菱角提取物对SMMC-7721细胞的增殖抑制作用;丫啶橙染色、DNA琼脂糖凝胶电泳和流式细胞仪检测细胞凋亡。[结果]菱角提取物能抑制SMMC-7721细胞的增殖,且呈明显的剂量依赖性。荧光显微镜下细胞呈典型的凋亡形态学改变。[结论]菱角提取物可抑制SMMC-7721细胞的增殖并诱导其凋亡。     

Differential Suppression of Human Cervical Cancer Cell Growth by Adenovirus Delivery of p53 in vitro: Arrest Phase of Cell Cycle Is Dependent on Cell Line

It has been reported that overexpression of wild-type p53 protein induces suppression of tumor cell growth in vivo and in vitro. In this study, we further evaluated the differential effects of p53 delivered in an adenovirus vector on the cell growth, apoptosis and cell cycle progression in cervical cancer cell lines. We constructed a recombinant adenovirus expressing p53 and then delivered this into cervical carcinoma cell lines (CaSki, SiHa, and HeLa, HeLaS3) along with adenovirus expressing β-galactosidase as a negative control. Adenovirus-delivered p53 overexpression resulted in a more significant suppression of cell growth in HPV 18-infected cells (HeLa and HeLaS3) and a lesser suppression in HPV 16-infected cells (CaSki and SiHa). However, no suppression was observed in cells infected with a negative control virus. p53 overexpression also induced apoptosis and cell cycle arrest, as determined by annexin V and propidium iodide staining. In particular, the cell cycle was arrested in the G₂/M phase in CaSki cells. In contrast, cell cycles were arrested in the G₁ phase in HeLa cells, suggesting that the arrest phase is dependent upon the cervical cancer cell line. Taken together, these data support the idea that overexpressed p53 protein plays a differential role in suppressing cervical cancer cell growth through apoptosis and cell cycle arrest in either G₁ or G₂/M phase, depending on the cancer cell line.     

Anti-hepatoma cells function of luteolin through inducing apoptosis and cell cycle arrest

The aim of this study is to explore the apoptotic induction and cell cycle arrest function of luteolin on the liver cancer cells and the related mechanism. The liver cancer cell line SMMC-7721, BEL-7402, and normal liver cells HL-7702 were treated with different concentrations of luteolin. Cell proliferation ability was tested. Morphological changes of the apoptotic cells were observed under inverted fluorescence microscope after Hoechst33342 staining. We investigated the effect of luteolin on cell cycling and apoptosis with flow cytometry. The mitochondrial membrane potential changes were analyzed after JC-1 staining. Caspases-3 and Bcl-2 family proteins expression were analyzed by real-time PCR. Cell proliferation of SMMC-7721 and BEL-7402 were inhibited by luteolin, and the inhibition was dose–time-dependent. Luteolin could arrest the cells at G1/S stage, reduce mitochondrial membrane potential, and induce higher apoptosis rate and the typical apoptotic morphological changes of the liver carcinoma cells. Q-RT-PCR results also showed that luteolin increased Bax and caspase-3 expression significantly and upregulated Bcl-2 expression in a dose-dependent manner in liver carcinoma cells. However, the normal liver cells HL-7702 was almost not affected by luteolin treatment. Luteolin can inhibit SMMC-7721 and BEL-7402 cell proliferation in a time- and dose-dependent manner. And the mechanism maybe through arresting cell cycle at phase G1/S, enhancing Bax level, reducing anti-apoptotic protein Bcl-2 level, resulting in activating caspase-3 enzyme and decrease of mitochondrial membrane potential, and finally leading to cell apoptosis.     

Cytostatic Effect of Deoxyspergualin on a Murine Leukemia Cell Line L1210

The mode of antiproliferative action of deoxyspergualin (NKT-01) was examined. The growth-inhibitory effect on a murine leukemia cell line L1210 following treatment with NKT-01 was time-dependent, and there was little or no effect on the syntheses of DNA and RNA. Thus, the inhibitory activity of NKT-01 was not attributable to the inhibition of DNA and RNA syntheses. The influence of NKT-01 on cell cycle progression was studied by flow cytometric analysis. Bromodeoxyuridine/DNA distribution patterns in cells that were treated for 72 h, showed that the growth inhibition is due to the delay of cell cycle progression but not to cytotoxicity. This finding was also supported by evidence that the treated cells were re-proliferative in fresh medium. In addition, a majority of drug-treated cells was prevented from traversing from the G₀/G₁ phase to the S phase by 144 h or longer exposure to NKT-01. The results suggest that NKT-01 is cytostatic, preventing G₀/G₁-S progression.     

Therapeutic Drug Monitoring of Etoposide in a 14-Day Infusion for Non-small-cell Lung Cancer

We investigated whether a constant plasma concentration could be obtained by the individualized administration of low-dose, prolonged-infusional etoposide. Etoposide was infused for 14 days at 40 mg/m²day initially in patients with inoperable non-small-cell lung cancer. The infusion rate was modified based upon the etoposide concentration at 24 h following the initiation of the infusion (C₂₄) to achieve a target concentration of 1.5 μg/ml. We postulated that severe toxicities could be avoided by maintaining the steady-state concentration at less than 2 7mu;g/ml, while antitumor activity could be expected if the steady-state concentration was maintained at more than 1 μg/ml. In a total of 21 courses in 12 patients, the mean etoposide dose was 35±6 mg/m² daily. The C₂₄ was 1.8±0.4 μg/ml and ranged from 1.1 to 2.9 μg/ml. Following dose modification, the mean concentration from 96 to 336 h (C_mean) was 1.6±0.2 μg/ml and ranged from 1.2 to 2.0 μg/ml. The toxicities were well-tolerated except for one patient with WHO grade 4 leukopenia and neutropenia who developed infectious complications. There were no treatment-related deaths. Following dose modification, the inter-patient variability was decreased successfully. Although this pharmacologically-guided method needs to be validated using more patients, it could be used for therapeutic drug monitoring.     

Induction of Programmed Death/Apoptosis in Androgen-dependent Mouse Mammary Tumor Cell Line (Shionogi Carcinoma 115) by Androgen Withdrawal

Shionogi Carcinoma 115 (SC 115) cells are a cloned cell line derived from androgen-dependent mouse mammary tumor. They can grow in serum-free culture if a physiological level of androgen is present in the medium, but can not proliferate in culture without testosterone. In the present study, the mechanism of cell death in SC 115 cells after androgen withdrawal was examined . Based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability, androgen withdrawal induces programmed cell death (apoptosis) of SC 115 cells in serum-free culture. Northern blot analysis was used to identify a series of genes whose expression per cell is enhanced during the recruitment of cells from a nonproliferative (i.e. G₀) state into G₁ (i.e., cyclins Dl and C), from G₁ into the S phase of the cell cycle (i.e., cdk2), and during the programmed cell death pathway (i.e. testosterone repressed prostatic message-2 (TRPM-2), transforming growth factor-β1 (TGF-β1) and glucose regulated 78 kilodalton protein (GRP-78)). Expression of TRPM-2, TGF-β1, GRP-78, and calmodulin genes increases, but that of cyclins C and Dl, and cdk2 genes decreases during programmed cell death of SC 115 cells. These results demonstrate that androgen-dependent SC 115 cells undergo programmed cell death induced by androgen withdrawal, and that this death does not require proliferation or progression into Gi of the proliferative cell cycle. SC 115 cells should be a good model for investigating programmed death of hormone-dependent cancer.     

Long-lasting Accumulation of Vinblastine in Inostamycin-treated Multidrug-resistant KB Cells

Inostamycin, a novel polyether compound, reverses multidrug resistance in KB cells. The mechanism of its action was studied by use of radioactively labeled vinblastine. Inostamycin dose-dependently increased the accumulation of [³H] vinblastine in multidrug-resistant KB-C4 cells at 0.5-2 μg/ml, while it did not enhance accumulation in the drug-sensitive KB-3-1 cells. At a concentration of 1 μ/ ml inostamycin inhibited active [³H] vinblastine efflux from KB-C4 cells, but not from KB-3-1 cells, and inhibited [³H] vinblastine binding to KB-C4 membranes with an IC_5O of 0.94 μg/ml (1.3 μ M ). Furthermore, [³H] vinblastine accumulated by treatment with 1 /μg/ml of inostamycin was resistant to efflux from KB-C4 cells, even after the removal of inostamycin.     

氯化镉和顺铂联合对人肝癌细胞增殖的抑制作用

背景与目的： 研究氯化镉和顺铂联合对人肝癌细胞SMMC-7721增殖的抑制作用。 材料与方法： 采用MTT法测定不同浓度氯化镉和顺铂对人肝癌细胞SMMC-7721增殖的抑制作用;应用两药相互作用指数进行联合作用分析。 结果： 0.56、1.12、2.25 μg/ml的氯化镉联合0.25、0.5、1.0 μg/ml的顺铂可协同抑制SMMC-7721增殖,且随着作用时间延长,协同抑制作用增强(P<0.05或 P<0.01)。 结论： 氯化镉与顺铂联合应用可以协同抑制人肝癌细胞SMMC-7721的增殖。     

复方苦参注射液联合奥沙利铂对人肝癌细胞株ＳＭＭＣ-７７２１增殖与凋亡的影响

目的　通过观察复方苦参注射液、奥沙利铂（ＯＸＡ）及其两药联合对人肝癌细胞株ＳＭＭＣ-７７２１增殖与凋亡的影响,探讨中药与化疗药物联合应用的协同增效作用。方法　采用ＭＴＴ法观察复方苦参注射液、ＯＸＡ及其两药联合对ＳＭＭＣ-７７２１细胞增殖的影响;应用流式细胞术分析对细胞周期的影响;采用原位末端标记法（ＴＵＮＥＬ）和荧光染色法观察对细胞凋亡的作用。结果　复方苦参注射液和ＯＸＡ对ＳＭＭＣ-７７２１细胞均有明显的抑制增殖作用,该作用随着药物作用时间的延长、剂量的增加而逐渐增强（Ｐ＜００１）;两药联合表现为相加或协同作用,与单药比较,有显著性差异（Ｐ＜０.０５）。ＴＵＮＥＬ法检测结果表明,复方苦参注射液（２５μｌ／ｍｌ）、ＯＸＡ（１μｇ／ｍｌ）以及两药联合作用于ＳＭＭＣ-７７２１细胞后均可诱导肝癌细胞凋亡,凋亡指数（ＡＩ）分别为２５.２％、１６.２％和３６.３％,联合组明显优于单药组（Ｐ＜０.０５）。流式细胞术分析显示,复方苦参注射液、ＯＸＡ均可使细胞被阻滞于Ｇ０／Ｇ１期,两药联合较单药更为显著（Ｐ＜０.０５）。结论　复方苦参注射液、ＯＸＡ均能抑制人肝癌细胞株ＳＭＭＣ-７７２１的增殖和诱导细胞凋亡,将细胞阻滞于Ｇ０／Ｇ１期,两药联合后作用加强,提示复方苦参注射液和ＯＸＡ联合应用治疗肝癌可能会起到协同增效的作用。     

γ-Irradiation Deregulates Cell Cycle Control and Apoptosis in Nevoid Basal Cell Carcinoma Syndrome-derived Cells

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that γ-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH , was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G₂M phase after γ-irradiation, whereas normal cells showed cell cycle arrest both in the G₀G₁ and G₂M phases. The fraction of apoptotic cells after γ-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after γ-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS.