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背景与目的:肿瘤细胞对抗癌药物产生耐受性是化疗失败的主要原因,突变型p53基因与肿瘤多药耐药密切相关。本研究旨在探讨腺病毒介导的p53基因(Ad-p53)对人乳腺癌多柔比星(阿霉素)耐药细胞株MCF-7/Adr多药耐药的逆转作用及其对耐药相关蛋白P-gp、TOPOⅡ和GST-π表达的影响。方法:以人乳腺癌MCF-7细胞及其多柔比星耐药株MCF-7/Adr为实验对象,cck-8法观察Ad-p53对多药耐药的逆转作用,Western blot检测P-gp、TOPOⅡ和GST-π蛋白表达的变化。结果:50MOI Ad-p53能使多柔比星对MCF-7/Adr细胞IC50由(4.54±0.91)μg/ml降到(0.26±0.11)μg/ml,逆转耐药倍数为18.1倍(P<0.001);P-gp、GST-π蛋白表达量下降,TOPOⅡ未见明显变化。结论:Ad-p53能够逆转MCF-7/Adr多药耐药,下调P-gp和GST-π表达。
BACKGROUND & OBJECTIVE: Tolerance of tumor cells to anticancer drugs is the main reason of chemotherapy failure. Mutant p53 gene is closely related to tumor multidrug resistance. This study aimed to investigate the reversal effect of adenovirus-mediated p53 gene (Ad-p53) on multidrug resistance in human breast cancer cell line ADM-7 / Adr and its resistance to multidrug resistance Effect of P-gp, TOPOⅡ and GST-π expression on drug-related proteins. Methods: Human breast cancer MCF-7 cells and multi-drug resistant strains MCF-7 / Adr were used as experimental subjects. The reversal effect of Ad-p53 on multidrug resistance was observed by cck-8 method. gp, TOPO Ⅱ and GST-π protein expression changes. Results: The IC50 of doxorubicin on MCF-7 / Adr cells was decreased from (4.54 ± 0.91) μg / ml to (0.26 ± 0.11) μg / ml with 18.5-fold reversal of drug resistance by 50 MOI Ad-p53 0.001). The expression of P-gp and GST-π protein decreased but there was no obvious change in TOPOⅡ. Conclusion: Ad-p53 can reverse multidrug resistance of MCF-7 / Adr and down-regulate the expression of P-gp and GST-π.