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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。
AIM: Tumor multidrug resistance (MDR) is one of the major causes of tumor chemotherapy failure and patient mortality. The development of a non-toxic MDR reversal agent is an exploratory study to cure tumors. The aim of this study was to investigate the reversal effect of two sildenafil homologs on the drug resistance of human breast cancer MCF-7 / ADR cells. Methods MTT assay was used to detect the effects of sildenafil, sildenafin homologues, doxorubicin and sildenafil homologues and doxorubicine on human breast cancer cell line MCF-7 / ADR and susceptible strains MCF-7 inhibition rate and IC50 value; using flow cytometry were observed Sildenafil homologue treatment, human breast cancer MCF-7 / ADR Rhodamine 123 cells in the concentration changes, and analysis of the two homologous Effect of P-gp protein efflux function on breast cancer cells. Results The MTT results showed that the reversal multiples of resistance to MCF-7 / ADR cells by 10 μmol / L of two sildenafil homologues were 6.36 and 5.58, respectively. Two sildenafil 20 μmol / 7 / ADR cells were 11.83 and 13.47, respectively. The results of flow cytometry showed that the concentration of Rhodamine 123 in MCF-7 / ADR cells treated with 10 and 20 μmol / L sildenafin was significantly increased . Conclusions Sildenafil homologs can inhibit the efflux of P-gp in breast cancer MCF-7 / ADR cells and reverse the drug resistance of doxorubicin.