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目的筛选HER2高表达乳腺癌细胞化疗耐受的药物种类,探讨HER2介导的乳腺癌多药耐药的机制。方法构建HER2稳定高表达的乳腺癌细胞MCF-7/HER2模型;MTT法检测该细胞对多种临床常用的抗乳腺癌药物的敏感性;Hochest33258染色观察药物诱导的MCF-7/HER2的凋亡率,并采用聚合酶链式反应(RT-PCR)检测细胞中bcl-2和survivin基因的mRNA表达。结果MCF-7/HER2细胞对Taxol,MMC,5-FU,VP-16及TSPA的耐药指数分别为对照细胞的74,22,2.5,3.5和2.8倍,出现了明显的药物抗性(P<0.05);而对CDDP,ADM,VBL,VCR,NBV和MTX等的耐药指数与对照组相比,差异无统计学意义(P>0.05);由Taxol,MMC,5-FU,VP-16诱导的MCF-7/HER2细胞凋亡率明显低于对照细胞;MCF-7/HER2细胞survivin基因表达明显高于对照组,而bcl-2基因表达与对照组比较,差异无统计学意义。结论HER2可介导乳腺癌细胞对Taxol,MMC,5-FU,VP-16和TSPA等的多药抗性,这种多药抗性的产生可能与HER2上调survivin表达所致的凋亡抗性有关。
Objective To screen the chemotherapeutic drug-resistant types of HER2-overexpressing breast cancer cells and to explore the mechanism of HER2-mediated multidrug resistance in breast cancer. Methods The MCF-7 / HER2 model of breast cancer cells with stable expression of HER2 was constructed. The sensitivity of the cells to various clinical anti-breast cancer drugs was tested by MTT assay. The apoptosis of MCF-7 / HER2 cells induced by drugs was observed by Hochest33258 staining The mRNA expression of bcl-2 and survivin in cells was detected by polymerase chain reaction (RT-PCR). Results The resistance index of MCF-7 / HER2 cells to Taxol, MMC, 5-FU, VP-16 and TSPA were 74,22,2.5,3.5 and 2.8 times higher than that of control cells, respectively. (P <0.05). The drug resistance index of CDDP, ADM, VBL, VCR, NBV and MTX were not significantly different from the control group (P> 0.05) 16 induced MCF-7 / HER2 cells apoptosis rate was significantly lower than the control cells; MCF-7 / HER2 cell survivin gene expression was significantly higher than the control group, while the bcl-2 gene expression compared with the control group, the difference was not statistically significant. Conclusion HER2 can mediate multidrug resistance of Taxol, MMC, 5-FU, VP-16 and TSPA in breast cancer cells. This multidrug resistance may be associated with HER2 up-regulation of apoptosis induced by survivin related.