乳腺癌耐药细胞株MCF-7/DOX中过表达miR-34c调节多柔比星敏感性的研究

Overexpression of miR-34c regulates the sensitivity to doxorubicin in drug-resistant breast cancer cell lines MCF-7/DOX

目的:研究乳腺癌耐药细胞株MCF-7/DOX中过表达miR-34c对多柔比星敏感性的调节作用。方法:培养乳腺癌细胞株MCF-7和乳腺癌耐药细胞株MCF-7/DOX,转染miR-34c及阴性对照片段,用不同剂量多柔比星处理;取处理后的细胞,用CCK-8试剂盒测定细胞活力、RNA检测试剂盒测定耐药相关基因的mRNA含量。结果:MCF-7/DOX细胞株中miR-34a、34b、34c的表达量均低于MCF-7细胞株且miR-34c表达量的下调最为显著,MDR1、BCRP、UCP2、Twist、c-Src的mRNA含量显著高于MCF-7细胞株;转染miR-34c后,多柔比星对MCF-7/DOX细胞株活力的抑制效应强于转染阴性对照的MCF-7/DOX细胞株,MDR1、BCRP、UCP2、Twist、c-Src的mRNA含量显著低于转染阴性对照的MCF-7/DOX细胞株。结论:乳腺癌耐药细胞株MCF-7/DOX中过表达miR-34c能够增加多柔比星敏感性,抑制耐药相关基因MDR1、BCRP、UCP2、Twist、s-Src的表达量。

Objective： To study the regulating effect of overexpression of miR-34c on the sensitivity to doxorubicin in drug-resistant breast cancer cell line MCF-7/DOX. Methods： Breast cancer cell lines MCF 7 and drug resistant breast cancer cell lines MCF-7/DOX were cultured, transfected with miR-34c and negative control fragments and treated with different doses of doxorubiein. Treated cells were taken, CCK-8 kits were used to detect eell viability, and RNA detection kits were used to detect mRNA contents of drug resistance-related genes. Results.. miR 34a, 34b and 34c expression levels in MCF-7/DOX cell lines were lower than those in MCF-7 cell lines and the reduction of miR-34e expression level was the most significant, mRNA contents of MDR1, BCRP, UCP2, Twist and c-Src were significantly higher than those in MCF-7 eell lines. After transfeetion of miR-34c, the inhibitory effect of doxorubiein on the viability of MCF-7/DOX eell lines was stronger than that of MCF-7/ DOX cell lines transfeeted with negative control, and mRNA contents of MDR1, BCRP, UCP2, Twist and e-Sre were significantly lower than those in MCF-7 cell lines transfeeted with negative control. Conclusion： Overexpression of miR-34c in drugresistant breast cancer cell lines MCF-7/DOX can increase the sensitivity to doxorubicin and inhibit the expression levels of drug resistance-related genes MDR1, BCRP, UCP2, Twist and c-Src.