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1.
??OBJECTIVE To investigate the mechanism of nucleophosmin (NPM) in the formation of breast cancer drug resistance. METHODS The methotrexate- resistant breast cancer cells (MCF-7/MTX) was established by escalating the concentrations of methotrexate to drug-sensitive MCF-7 cells (MCF-7/S). The cells viability of MCF-7/MTX was detected by MTT test, cell growth curve was drawn and doubling time was calculated. The cell morphology and ultrastructure were observed using optical and transmission electron microscopy. The expression of NPM and factors related to drug resistance were tested by Real-time PCR and Western blot assay. Then the NPM level was attenuated by RNA interfering technology, and the resistance mechanism was explored in MCF-7/MTX cells. RESULTS The MCF-7/MTX cell line was successfully established and resistance factor was 64. The resistant cells has spindle shaped morphology and tended to grow slowly, and the variations appeared in the internal structure of cells. MCF-7/MTX cells possessed cross-resistance to various chemotherapeutic drugs. The expressions of NPM and multidrug-resistant factors P-gp, MRP1, BCRP were up-regulated in the resistant cells. Further, the overexpression of NPM activated PI3K/Akt signaling pathway and inhibited downstream apoptotic factors. Then knockdown of NPM by siRNA significantly decreased the drug resistance of MCF-7/MTX cells, suppressed PI3K/Akt pathway and promoted the downstream cells apoptosis. CONCLUSION The high expression of NPM has an important role in the formation of breast cancer drug resistance, and it is expected to be a novel molecular target for breast cancer treatment in clinical. 相似文献
2.
Keisuke Nakashima Nantiga Virgona Mio Miyazawa Takashi Watanabe Tomohiro Yano 《Phytotherapy research : PTR》2010,24(9):1317-1321
Resistance to chemotherapy (chemoresistance) is a serious problem in malignant mesothelioma, a highly aggressive neoplasm. Gamma‐tocotrienol (γ‐T3) can sensitize various cancerous cells to chemotherapeutic agents by inhibiting pathways that lead to treatment resistance. In this study, we investigated the modulating effect of tocotrienol‐rich fraction (TRF) from rice bran, which is abundant in γ‐T3, on chemoresistance in human MM H28 cells. TRF treatment caused a marked reduction in the viability of H28 cells in a dose‐dependent manner, while cisplatin treatment had no effect on the cells, indicating that H28 cells are resistant to cisplatin. A significant increase in cytotoxicity was observed in H28 cells treated with TRF, and this effect was enhanced by the combination treatment with cisplatin. The cytotoxic effect was closely related to the inhibition of phosphatidylinositol 3‐kinase (PI3K)‐AKT signaling. Inactivation of Akt signaling by TRF or the combination with cisplatin mitigated cisplatin‐induced activation of Akt, resulting in reducing the chemoresistance H28 cells to cisplatin. Reduced cell viability and attenuated chemoresistance of the H28 cells against cisplatin were also observed following the use of a PI3K inhibitor, LY294002. These results suggest that the combination therapy of cisplatin with TRF is a plausible strategy for achieving tolerance for the chemotherapeutic agent in MM therapy. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
3.
Xiao‐Zhong Liao Ying Gao Ling‐Ling Sun Jia‐Hui Liu Han‐Rui Chen Ling Yu Zhuang‐Zhong Chen Wen‐Hui Chen Li‐Zhu Lin 《Phytotherapy research : PTR》2020,34(5):1142-1153
Cisplatin (DDP) is one of the first‐line chemotherapeutic agents for non‐small cell lung cancer (NSCLC). However, repeated use of cisplatin in clinical practice often induces chemoresistance. The aims of this study were to investigate whether rosmarinic acid (RA) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms. Our data demonstrated that RA significantly inhibited NSCLC cell proliferation and cell colony formation in a dose‐dependent manner, induced G1 phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to DDP. Mechanistically, RA inhibited NSCLC cell growth, arrested cell cycle, and induced apoptosis by activating MAPK and inhibiting the expression of P‐gp and MDR1, which correspondingly enhanced p21 and p53 expression. We observed that the growth of xenograft tumors derived from NSCLC cell lines in nude mice was significantly inhibited by combination therapy. We demonstrate that RA is a potentially effective MDR reversal agent for NSCLC, based on downregulation of MDR1 mRNA expression and P‐gp. Together, these results emphasize the putative role of RA as a resistance reversal agent in NSCLC. 相似文献
4.
目的 探讨吴茱萸碱(evodiamine,EVO)对白血病K562细胞及其耐药株K562/Adr的增殖、细胞周期及多药耐药性(MDR)的影响。方法用细胞增殖毒性检测试剂盒(CCK-8)检测EVO和/或柔红霉素(DNR)对细胞增殖的影响,并计算耐药指数(RI)和逆转倍数(RF);流式细胞仪检测EVO和/或DNR对K562及K562/Adr细胞周期的影响;流式细胞仪检测K562及K562/Adr细胞内DNR的荧光强度;定量PCR检测K562及K562/Adr细胞中MDR1基因的表达;Western blotting检测K562及K562/Adr细胞中MDR1、BCRP蛋白的表达。结果EVO、DNR作用于K562和K562/Adr细胞后,细胞增殖受到抑制,且呈剂量和时间依赖性;与K562细胞相比,K562/Adr细胞对DNR的RI为30.54,K562/Adr细胞对EVO的RI为19.09。当EVO(0.125 gmol/L)与不同浓度DNR联合作用后,能使DNR对K562/Adr细胞的IC_(50)明显下降,DNR+EVO对K562/Adr细胞的RF为12.07;EVO、DNR单独或联合作用于K562及K562/Adr细胞后,能够使K562/Adr细胞BCRP、MDR1蛋白及mRNA表达水平均明显下降。结论EVO能有效逆转白血病K562/Adr细胞对DNR的耐药现象,而这种作用可能与EVO通过减少细胞膜上多药耐药蛋白MDR1的表达有关。 相似文献
5.
Xiao‐Zhong Liao Ying Gao Sheng Huang Zhuang‐Zhong Chen Ling‐Ling Sun Jia‐Hui Liu Han‐Rui Chen Ling Yu Jia‐Xing Zhang Li‐Zhu Lin 《Phytotherapy research : PTR》2019,33(9):2298-2309
Cisplatin represents one of the first‐line drugs used for non‐small‐cell lung cancer treatment. However, considerable side effects and the emergence of drug resistance are becoming critical limitations to its application. Combinatorial strategies may be able to extend the use of cisplatin. Both Tanshinone IIA and cisplatin inhibit non‐small‐cell lung cancer cell growth in a time‐ and dose‐dependent manner. When Tanshinone IIA was combined with cisplatin at a ratio of 20:1, they were observed to exert a synergistic inhibitory effect on non‐small‐cell lung cancer cells. The combination treatment was shown to impair cell migration and invasion, arrest the cell cycle in the S phases, and induce apoptosis in A549 and PC9 cells in a synergistic manner. KEGG pathway analysis and molecular docking indicated that Tanshinone IIA might mainly influence the phosphatidylinositol 3‐kinase‐Akt signalling pathway. In all treated groups, the expression levels of Bax and cleaved Caspase‐3 were up‐regulated, whereas the expression levels of Bcl‐2, Caspase‐3, p‐Akt, and p‐PI3K proteins were down‐regulated. Among these, the combination of Tan IIA and cisplatin exhibited the most significant difference. Tanshinone IIA may function as a novel option for combination therapy for non‐small‐cell lung cancer treatment. 相似文献
6.
??OBJECTIVE To investigate the effects of interferon-??(IFN-??) and all-trans retinoic acid(ATRA) on multidrug resistance reversal effect and mechanism of human leukemia K562/ADM cells. METHODS The cytotoxicity and reversal times of IFN-?? and ATRA were detected by CCK-8 method. Apoptosis rate and cell cycle were detected by flow cytometry. PI3K, Akt and Bad mRNA were detected by RT-PCR method. Western blot method was used to detect the expression of PI3K, AKt, P-AKt and Bad protein.RESULTS The drug resistance of K562/ADM cells to adriamycin(ADM) was 54 times. ADM, respectively, with IFN-??, ATRA or combined application, the drug resistance of K562/ADM cells to ADM was 1.24, 2.34 and 8.14, respectively. The apoptosis rate of K562/ADM cells was significantly increased by using ADM 4 mg??L-1alone or in combination with IFN-?? 2.5??106 U??L-1, ATRA 7.5 ??mol??L-1, and the cell cycle was blocked in G0/G1 phase. PI3K mRNA and protein expression were significantly lowered, Akt mRNA and protein has no obvious change, Bad mRNA and protein expression are raised, phosphorylated Akt protein expression decreased, the expression is more obvious when the two drug combination. CONCLUSION IFN-?? and ATRA can reverse the multidrug resistance of K562/ADM cells, its mechanism may be the inhibition of the PI3K/Akt pathway. 相似文献
7.
Astragaloside IV inhibits TGF‐β1‐induced epithelial‐mesenchymal transition through inhibition of the PI3K/Akt/NF‐κB pathway in gastric cancer cells
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Astragaloside IV (AS‐IV) has been reported to possess anti‐metastasis activity in cancer cells. However, it is unknown whether AS‐IV could inhibit epithelial‐mesenchymal transition (EMT), a cellular de‐differentiation program that promotes metastasis, in cancer cells. The aim of this study was to study the effect and mechanism of AS‐IV on EMT in gastric cancer (GC) cells. The results showed that AS‐IV significantly inhibited cell viability, invasion, and migration of GC cells. The E‐cadherin to N‐cadherin switch and expression of Vimentin and metastasis‐related genes were induced by transforming growth factor β1 (TGF‐β1), whereas AS‐IV reversed the induction. In addition, AS‐IV inhibited TGF‐β1‐induced activation of PI3K/Akt/NF‐κB. Inhibition of the PI3K/Akt/NF‐κB pathway reversed TGF‐β1‐induced EMT. In conclusion, AS‐IV inhibited TGF‐β1‐induced EMT through inhibition of the PI3K/Akt/NF‐κB pathway in GC cells. AS‐IV might be an effective candidate for the treatment for GC. 相似文献
8.
Ki Dong Kim Dongwoo Nam Bum Sang Shim Sung‐Hoon Kim Kyoo Seok Ahn Seung‐Hoon Choi Kwang Seok Ahn 《Phytotherapy research : PTR》2014,28(3):423-431
The oncogenic PI3K/Akt/mammalian target of rapamycin (mTOR) signaling axis and its downstream effector, the ribosomal protein S6 kinase 1 (S6K1) play a key role in mediating cell survival in various tumor cells. Here, we investigated the effects of brassinin (BSN), a phytoalexin first identified as a constituent of cabbage, on the PI3K/Akt/mTOR/S6K1 activation, cellular proliferation, and apoptosis in PC‐3 human prostate cancer. BSN exerted a significant dose‐dependent cytotoxicity and reduced constitutive phosphorylation of Akt against androgen‐independent PC‐3 cells as compared to androgen‐dependent LNCaP cells. Moreover, knockdown of androgen receptor (AR) by small interfering RNA enhanced the potential effect of BSN on induction of apoptosis in LNCaP cells. BSN clearly suppressed the constitutive activation of PI3K/Akt/mTOR/S6K1 signaling cascade, which correlated with the induction of apoptosis as characterized by accumulation of cells in subG1 phase, positive Annexin V binding, TUNEL staining, loss of mitochondrial membrane potential, down‐regulation of antiapoptotic and proliferative proteins, activation of caspase‐3, and cleavage of PARP. Additionally, BSN could block broad‐spectrum inhibition of PI3K/Akt/mTOR/S6K1 axes, and aberrant Akt activation by pcDNA3‐myr‐HA‐Akt1 plasmid could not prevent the observed suppressive effect of BSN on constitutive mTOR activation. Finally, overexpression of Bcl‐2 also attenuated BSN‐mediated apoptosis in PC‐3 cells. Taken together, our findings suggest that BSN can interfere with multiple signaling cascades involved in tumorigenesis and might be provided as a potential therapeutic candidate for both the prevention and treatment of prostate cancer. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
9.
Paris saponin VII induces cell cycle arrest and apoptosis by regulating Akt/MAPK pathway and inhibition of P‐glycoprotein in K562/ADR cells
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Ting Yan Gaosheng Hu Anhua Wang Xianduo Sun Xiangyong Yu Jingming Jia 《Phytotherapy research : PTR》2018,32(5):898-907
Paris saponinVII (PSVII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. We found that PSVII could inhibit the growth of adriamycin‐resistant human leukemia cells (K562/ADR) in a dose‐dependent manner. Furthermore, the molecular mechanism underlying the cytotoxicity and downregulation of P‐glycoprotein (P‐gp) expression by PSVII was clarified. PSVII significantly suppressed cell proliferation by cell cycle arrest in the G0/G1 phase, which was associated with an obvious decrease in cyclin B1/D1 and CDK2/4/6 protein expression. Moreover, PSVII could attenuate mitochondrial membrane potential, increase the expression of apoptosis‐related proteins, such as Bax and cytochrome c, and decrease the protein expression levels of Bcl‐2, caspase‐9, caspase‐3, PARP‐1, and p‐Akt. We also found that JNK, ERK1/2, and p38 were regulated by PSVII in K562/ADR cells. And further studies indicated that the decrease in the reactive oxygen species level inhibited intrinsic P‐gp expression. Therefore, PSVII‐induced apoptosis in K562/ADR cells was associated with Akt/MAPK and the inhibition of P‐gp. In addition, PSVII induced a robust autophagy in K562/ADR cells as demonstrated by the degradation of LC3‐I. These results provide a biochemical basis for possible clinical applications of PSVII in the treatment of leukemia. 相似文献
10.
Caffeoylserotonin (CaS) has strong radical scavenging activity as well as antioxidant activities, protecting cells from lipid peroxidation, intracellular reactive oxygen species generation, DNA damage, and cell death. The molecular mechanism by which CaS protects against oxidative stress is not well understood. Here, we analyzed the cytoprotective activity of CaS in hydrogen peroxide (H2O2)‐treated keratinocyte HaCaT cells. H2O2 induced apoptosis in the cells through activation of pro‐apoptotic p21, Bax, and caspase‐3. Pretreatment with CaS inhibited apoptotic gene expression and activated the anti‐apoptotic gene, Bcl‐xL. Although CaS did not directly affect heme oxygenase‐1 (HO‐1) expression, pretreatment with CaS augmented HO‐1 expression through an increase in NF‐E2‐related factor (Nrf2) stability and stimulation of Nrf2 translocation to the nucleus upon H2O2 exposure. H2O2 also induced the phosphorylation and subsequent activation of ERK, p38 MAPK, and Akt. Analysis using specific inhibitors of p38 MAPK and Akt demonstrated that only Akt activation was involved in HO‐1 and Nrf2 expressions. In addition, PI3K and PKC inhibitors suppressed HO‐1/Nrf2 expression and Akt phosphorylation. These results demonstrate that CaS protects against oxidative stress‐induced keratinocyte cell death in part through the activation of Nrf2‐mediated HO‐1 induction via the PI3K/Akt and/or PKC pathways, but not MAPK signaling. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
11.
Decursin in Angelica gigas Nakai (AGN) Enhances Doxorubicin Chemosensitivity in NCI/ADR‐RES Ovarian Cancer Cells via Inhibition of P‐glycoprotein Expression
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Min Kyoung Kim Min Soo Kim Seung Hee Moon Il Hwan Kim Seong‐Gyu Ko 《Phytotherapy research : PTR》2016,30(12):2020-2026
Angelica gigas Nakai (AGN, Korean Dang‐gui) is traditionally used for the treatment of various diseases including cancer. Here, we investigated multidrug‐resistant phenotype‐reversal activities of AGN and its compounds (decursin, ferulic acid, and nodakenin) in doxorubicin‐resistant NCI/ADR‐RES ovarian cancer cells. Our results showed that a combination of doxorubicin with either AGN or decursin inhibited a proliferation of NCI/ADR‐RES cells. These combinations increased the number of cells at sub‐G1 phase when cells were stained with Annexin V‐fluorescein isothiocyanate. We also found that these combinations activated caspase‐9, caspase‐8, and caspase‐3 and increased cleaved PARP level. Moreover, an inhibition of P‐glycoprotein expression by either AGN or decursin resulted in a reduction of its activity in NCI/ADR‐RES cells. Therefore, our data demonstrate that decursin in AGN inhibits doxorubicin‐resistant ovarian cancer cell proliferation and induces apoptosis in the presence of doxorubicin via blocking P‐glycoprotein expression. Therefore, AGN would be a potentially novel treatment option for multidrug‐resistant tumors by sensitizing to anticancer agents. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
12.
Quercetin reversed MDR in breast cancer cells through down‐regulating P‐gp expression and eliminating cancer stem cells mediated by YB‐1 nuclear translocation
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Shizheng Li Qian Zhao Bo Wang Song Yuan Xiuyan Wang Kun Li 《Phytotherapy research : PTR》2018,32(8):1530-1536
Overexpression of P‐glycoprotein (P‐gp) plays an important role in mediating multidrug resistance (MDR), resulting in chemotherapy failure of tumor patients and enhancement of cancer stem cell characteristics. By preparing doxorubicin (Dox) resistant human breast cancer MCF‐7 cells, here, we wanted to evaluate the effects of quercetin (Que) on MDR reversal activity and investigate its possible mechanism. MCF‐7 and MCF‐7/dox cells were respectively treated by Dox, paclitaxel (Pac), or vincristine (Vcr) with or without Que intervention for 24 hr. Cell viability, cell apoptosis, cell cycle, intracellular drug accumulation, the expression of P‐gp and Y‐box binding protein 1 (YB‐1), and breast cancer stem cells (BCSCs) were then assessed. The results showed that Que significantly enhanced the antitumor activities of Dox, Pac, and Vcr in breast cancer cells. In addition, combined treatment of Dox, Pac, or Vcr with Que significantly downregulated P‐gp expression and eliminated BCSCs. Furthermore, combined treatment of Dox, Pac, or Vcr with Que significantly inhibited nuclear translocation of YB‐1. Thus, we speculated that Que reversed MDR in breast cancer cells through downregulating P‐gp expression and eliminating cancer stem cells mediated by YB‐1 nuclear translocation. 相似文献
13.
Youjun Luo Lin Zha Lumeng Luo Xue Chen Qi Zhang Caixia Gao Xibing Zhuang Sujuan Yuan Tiankui Qiao 《Phytotherapy research : PTR》2019,33(5):1353-1362
Cisplatin‐based chemotherapy is a widely used chemotherapeutic regimen for gastric cancer; however, drug resistance limits its efficacy. [6]‐Gingerol has been found to exhibit anticancer effects. Here, we aim to explore the potential of [6]‐gingerol in combination with cisplatin as a new regimen for gastric cancer. CCK‐8 assay and colony formation assay were used to determine the effect of [6]‐gingerol in combination with cisplatin on cell viability of gastric cancer cells. Flow cytometry was performed to assess cell cycle distribution. Wound‐healing assay and transwell invasion assay were conducted to examine the migration and invasion abilities. Cell cycle and invasion‐related proteins and mRNAs, as well as PI3K/AKT signaling proteins, were assessed by western blotting and quantitative real‐time polymerase chain reaction. Combination of [6]‐gingerol with cisplatin inhibited cell viability and enhanced cell cycle arrest at G1 phase compared with cisplatin alone. The combination treatment inhibited cell migration and invasion ability and decreased cyclin D1, cyclin A2, matrix metalloproteinase‐9, p‐PI3K, AKT, and p‐AKT protein expressions and increased P21 and P27 mRNA levels. Our study demonstrates that [6]‐gingerol enhances the cisplatin sensitivity of gastric cancer cells and that the mechanisms involve G1 phase arrest, migration and invasion suppression via PI3K/AKT signaling pathway. 相似文献
14.
Muhammad Imran Tanweer Aslam Gondal Muhammad Atif Muhammad Shahbaz Tahira Batool Qaisarani Muhammad Hanif Mughal Bahare Salehi Miquel Martorell Javad Sharifi‐Rad 《Phytotherapy research : PTR》2020,34(8):1812-1828
Apigenin is an edible plant‐derived flavonoid that has been reported as an anticancer agent in several experimental and biological studies. It exhibits cell growth arrest and apoptosis in different types of tumors such as breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach, by modulating several signaling pathways. Apigenin induces apoptosis by the activation of extrinsic caspase‐dependent pathway by upregulating the mRNA expressions of caspase‐3, caspase‐8, and TNF‐α. It induces intrinsic apoptosis pathway as evidenced by the induction of cytochrome c, Bax, and caspase‐3, while caspase‐8, TNF‐α, and B‐cell lymphoma 2 levels remained unchanged in human prostate cancer PC‐3 cells. Apigenin treatment leads to significant downregulation of matrix metallopeptidases‐2, ?9, Snail, and Slug, suppressing invasion. The expressions of NF‐κB p105/p50, PI3K, Akt, and the phosphorylation of p‐Akt decreases after treatment with apigenin. However, apigenin‐mediated treatment significantly reduces pluripotency marker Oct3/4 protein expression which might be associated with the downregulation of PI3K/Akt/NF‐κB signaling. 相似文献
15.
目的:研究解毒祛瘀方对人乳腺癌耐药细胞MCF-7/ADM耐药逆转的作用及机制。方法:以MCF-7/ADM细胞为研究对象,利用噻唑蓝(MTT)比色法检测解毒祛瘀方对人乳腺癌耐药细胞MCF-7/ADM生长的影响;应用流式细胞术检测肿瘤细胞内罗丹明123(Rh-123)的含量;分别利用实时荧光定量聚合酶链式反应(Real-time PCR)及蛋白免疫印迹法(Western blot)检测肿瘤细胞内多药耐药蛋白1(MDR1),乳腺癌耐药相关蛋白(BCRP)mRNA及蛋白表达变化。结果:与空白组比较,经1.25,2.5 g·L~(-1)解毒祛瘀方作用后,阿霉素对人乳腺癌耐药细胞MCF-7/ADM的逆转倍数(RF)分别提升1.7倍和3.0倍(P0.05);人乳腺癌耐药细胞MCF-7/ADM中Rh-123含量分别提高了1.8倍和2.5倍(P0.05),MDR1和BCRP蛋白和mRNA表达水平明显下降(P0.05),1.25,2.5 g·L~(-1)解毒祛瘀方MDR1 mRNA表达分别降低35.5%和56.0%(P0.05),BCRP mRNA表达分别降低41.6%和49.5%(P0.05)。结论:解毒祛瘀方可提高人乳腺癌耐药细胞MCF-7/ADM对阿霉素的敏感性,逆转该细胞对阿霉素的耐药性,其机制可能与降低MDR1和BCRP蛋白和mRNA的表达,抑制细胞药物外排作用相关。 相似文献
16.
目的探讨消岩汤含药血清对耐顺铂人肺腺癌A545659/DDP细胞多药耐药相关蛋白1(MRP1)、肺耐药蛋白(LRP)及其m RNA表达水平的影响,发现消岩汤对化疗耐药的作用靶点,为肺癌化疗耐药的临床治疗提供理论基础。方法 A549裸鼠皮下移植瘤模型ip给予等量生理盐水,2 mg/kg顺铂,消岩汤低、高剂量(20、40 g/kg)获得含药血清,选择耐顺铂人肺腺癌A549/DDP细胞系作为获得性耐药模型,采用Western blotting免疫印迹法及RT-PCR技术,检测各组含药血清作用下A549/DDP细胞多药耐药基因MRP1、LRP及其产物MRP1、LRP蛋白的表达水平。结果与对照组相比,随着血清中药物浓度的增加,消岩汤低、高剂量组LRP与MRP1蛋白表达逐渐减弱(P0.05)。LRP及MRP1 m RNA水平也有所下降(P0.05),且随着药物浓度的增加,基因表达抑制越明显。结论不同浓度的消岩汤含药血清对MRP1、LRP及其m RNA表达均具有不同程度的抑制作用,且浓度越高,抑制作用越明显,即与剂量呈正相关,揭示消岩汤逆转肺癌耐药可能与抑制MRP1和LRP蛋白功能有关。 相似文献
17.
Do Thi Ha Tran Thi Phuong Joonseok Oh KiHwan Bae Nguyen Duy Thuan MinKyun Na 《Phytotherapy research : PTR》2014,28(2):308-311
Paeonia suffruticosa has been traditionally employed for vitalizing blood circulation and alleviating liver and inflammatory diseases. The pathways by which palbinone (PB) isolated from P. suffruticosa mediates heme oxygenase‐1 (HO‐1) induction were investigated using the specific inhibitors for PI3K and mitogen activated protein kinases pathways. The effect of PB‐treatment on Nrf2 translocalization and HO‐1‐antioxidant response element (ARE) regulation was examined employing Western blot and luciferase assays. PB induced HO‐1 expression via the activation of Nrf2 in the hepatic cells, and ARE‐dependent genes were stimulated via the PB‐mediated Nrf2 activation. PB‐mediated HO‐1 expression could be involved with PI3K/Akt and ERK1/2 pathways. Our study suggests the mechanism by which PB induces HO‐1 expression in the hepatic cells. This might substantiate the traditional applications of P. suffruticosa for the treatment of oxidative stress‐related diseases including oxidant and inflammatory‐mediated vascular and liver diseases. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
18.
目的研究小檗胺诱导人白血病K562/Adr细胞凋亡及逆转多药耐药的作用及机理。方法采用MTT法测IC50值,流式细胞仪Annexin V FITC-PI法检测细胞凋亡发生率,PI染色法检测凋亡峰及细胞周期,同时以FCM检测Caspase-3、P-GP蛋白表达及细胞内药物积聚能力,RT-PCR法检测mdr-1基因表达。结果小檗胺能抑制人白血病K562/Adr细胞生长且呈剂量依赖关系,并能诱导细胞凋亡,使Caspase-3蛋白表达及细胞药物外排能力增加,同时降低mdr-1基因mRNA和蛋白表达水平。结论小檗胺能激活Caspase-3以诱导人白血病K562/Adr细胞凋亡,同时能通过降低mdr-1表达逆转多药耐药。 相似文献
19.
5,7‐Dihydroxy‐6‐Methoxy‐Flavonoids Eliminate HIV‐1 D3‐transfected Cytoprotective Macrophages by Inhibiting the PI3K/Akt Signaling Pathway
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Flavonoids, well‐documented secondary metabolites in many vegetables and plants, exhibit antiinflammatory, anti‐oxidant, anti‐microbial, and anticancer activities. However, their cytotoxic effects against human immunodeficiency virus type 1 (HIV‐1)‐infected cytoprotective macrophages have not been studied. In the present study, we investigated their effects and their molecular mechanisms. Treatment with flavonoids in the presence of lipopolysaccharide (LPS)/cycloheximide (CHX) potently eliminated HIV‐1 Tat‐transduced cytoprotective human microglial CHME5 cells; the 5,7‐dihydroxy‐6‐methoxy‐flavonoids oroxylin A and tectorigenin, at a concentration of 10 μM, most potently eliminated the cytoprotective phenotype. These flavonoids eliminated Tat‐transduced CHME5 cells, D3‐transfected CHME5 cells, and HIV‐1 D3‐infected human primary macrophages, in a dose‐dependent manner. Furthermore, oroxylin A and tectorigenin potently inhibited LPS/CHX‐induced phosphorylation of phosphoinositide 3‐kinase (PI3K), pyruvate dehydrogenase lipoamide kinase isozyme 1, Akt, and glycogen synthase kinase‐3β in the Tat‐transduced cells, D3‐transfected CHME5 cells, and D3‐infected human primary macrophages. Based on these findings, 5,7‐dihydroxy‐6‐methoxy‐flavonoids may eliminate HIV‐1 infected cytoprotective macrophages by inhibiting the PI3K/Akt signaling pathway and deliver anti‐HIV‐1 effects in vivo by shortening the lifespan of infected macrophages. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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Modulation of Multidrug Resistance Protein 2 Efflux in the Cisplatin Resistance Human Ovarian Carcinoma Cells A2780/RCIS by Sesquiterpene Coumarins
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Jamal Kasaian Fatemeh Mosaffa Javad Behravan Milena Masullo Sonia Piacente Mehrdad Iranshahi 《Phytotherapy research : PTR》2016,30(1):84-89
Recent in vitro studies showed that sesquiterpene coumarins (SCs) can be used as chemosensitizers. In this study, 14 SCs were isolated and purified from roots of four Ferula species and their structures were elucidated by spectroscopic methods. The purified SCs were evaluated for multidrug resistance (MDR) reversal properties in A2780/RCIS cells (cisplatin‐resistant derivatives of the human ovarian carcinoma cell line A2780P). Among the tested compounds, mogoltacin, mogoltadone, farnesiferol A, farnesiferol B, farnesiferol C, lehmferin, conferdione, and samarcandin showed significant MDR reversing effects. The combination of nontoxic concentrations of SCs (20 μM) with cisplatin enhanced cisplatin cytotoxicity on A2780/RCIS cells significantly. Flow cytometric efflux assay confirmed that the intracellular accumulation of 5‐carboxyfluorescein diacetate (5‐CFDA) was significantly increased in A2780/RCIS cells when treated with SCs. Our findings revealed that conferdione and samarcandin possessed the highest inhibitory effects on multidrug resistance‐associated protein 2 pump efflux, and therefore, these compounds could be considered as lead scaffolds for further structure modifications. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献