【摘要】 目的肿瘤多药耐药(multidrug resistance,MDR)是肿瘤化疗失败和患者死亡的一个主要原因,研发无毒的MDR逆转剂是治愈肿瘤的一项探索性研究。文中探讨2种西地那非同系物对人乳腺癌MCF-7/ADR细胞耐药性的逆转作用。方法采用MTT法检测西地那非、西地那非同系物、多柔比星以及西地那非同系物与多柔比星联合作用对人乳腺癌耐药细胞MCF-7/ADR和敏感株MCF-7的抑制率及IC50值;运用流式细胞术观察分别经西地那非同系物处理前后,人乳腺癌MCF-7/ADR细胞内Rhodamine 123浓度的改变情况,并分析该2种同系物对乳腺癌细胞P-gp蛋白外排功能的影响。结果 MTT结果显示10μmol/L的2种西地那非同系物对MCF-7/ADR细胞耐药性的逆转倍数分别是6.36和5.58;20μmol/L的2种西地那非同系物对MCF-7/ADR细胞耐药性的逆转倍数分别是11.83和13.47;流式细胞术结果显示经10、20μmol/L的西地那非同系物处理后的MCF-7/ADR细胞内Rhodamine 123浓度明显增强。结论一定浓度的西地那非同系物可抑制乳腺癌MCF-7/ADR细胞P-gp蛋的外排功能,并显著逆转其对多柔比星的耐药作用。更多还原

【Abstract】 Objective Multidrug resistance( MDR) of carcinoma is an important cause of chemotherapy failure and mortality in cancer patients. The aim of this study was to explore the reversal effect of XDNF1-0425 and XDNF8-0113 on Doxorubicin( DOX) resistance in human breast cancer cell line MCF-7 / ADR in vitro. Methods Using MTT assay,we determined the inhibitory effect of sildenafil,XDNF1-0425,XDNF8-0113,DOX and DOX + sildenafil homologues on the growth of human breast cancer cell lines MCF-7 and MCF-7 / ADR,and figured out the inhibitive concentration 50( IC50). We used flow cytometry to detect the concentration of rhodamine123 in the MCF-7 / ADR cells treated with XDNF1-0425 or XDNF8-0113 and analyzed its effect on P-gp-mediated drug efflux. Results The sensitivity of MCF-7 /ADR to DOX was significantly increased by the two sildenafil homologues XDNF1-0425 and XDNF1-0113 in a dose-dependent manner( P < 0. 05). XDNF1-0425 and XDNF1-0113 reversed the drug resistance of MCF-7 / ADR by 6. 36 and 5. 58 times at 10 μmol / L and by 11. 83 and 13. 47 times at 20 μmol / L,respectively. Flow cytometry showed significantly increased concentrations of rhodamine123 in the MCF-7 / ADR cells after treated with the two sildenafil homologues at 10 or 20 μmol / L. Conclusion Sildenafil homologues at a certain concentration can inhibit P-gp-mediated drug efflux of the human breast cancer cell line MCF-7 / ADR and effectively reverse its resistance to Doxorubicin.更多还原