目的：研究RNA干扰人抗原R（human antigen R，HuR）基因的表达对人乳腺癌耐药细胞株MCF-7/Adr对多柔比星（doxorubicin）敏感性的影响。 方法： 构建靶向 HuR基因 的shRNA表达质粒（pGenesil-siHuR），稳定转染至MCF-7/Adr细胞，real-time PCR检测细胞中 MDR1 mRNA的表达，Western blotting检测MCF-7/Adr细胞中由 MDR1 基因编码的P糖蛋白（P-glycoprotein,P-gp）的表达，MTT法检测pGenesil-siHuR 转染后MCF-7/Adr细胞在多柔比星作用后的存活率和IC50，流式细胞术检测MCF-7/Adr细胞的凋亡率。 结果： 与未转染的MCF-7/Adr细胞比较，pGenesil-siHuR质粒转染MCF-7/Adr细胞中 MDR1 mRNA的表达水平明显减低\[（0184±0.029） vs （1.203±0.026），P<0.01\]，P-gp表达水平明显降低。pGenesil-siHuR质粒转染MCF-7/Adr细胞后，MCF-7/Adr细胞对多柔比星的IC50从未转染的(148.2±2.3）nmol/L降至(42.9±0.4）nmol/L；经多柔比星处理后，pGenesil-siHuR质粒转染组MCF-7/Adr细胞的凋亡率明显上升\[（34.6±1.1）% vs （1.1±0.2）%，P<001\]。 结论： RNA干扰HuR的表达能抑制 MDR1基因 的表达，增加耐药乳腺癌MCF-7/Adr细胞对多柔比星的敏感性。

Objective: To investigate the effect of interference of human antigen R (HuR) expression on sensitivity of human multidrug-resistant human breast cancer MCF-7/Adr cell line to Doxorubicn. Methods: The shRNA expression vector targeting HuR gene (pGenesil-siHuR) has been constructed and stably transfected into human breast cancer MCF-7/Adr cell line. The expression level of MDR1 mRNA in MCF-7/Adr cells was assayed by real-time PCR. The P-gp protein (encoded by the MDR1 gene) expression were determined by Western blotting. The survival rate and IC50 of MCF-7/Adr cells to doxorubicin after pGenesil-siHuR transfection were evaluated by MTT method. The apoptosis rate of MCF-7/Adr cells was detected by flow cytometry. Results: Compared with untransfected MCF-7/Adr cells, the MDR1 mRNA（\[0.184±0.029\] vs \[1.203±0.026\]，P<0.01）and P-gp protein expressions（\[0.314±0.011\] vs \[0.796±0007\], P<0.01）were significantly reduced in pGenesil-siHuR transfected MCF-7/Adr cells (P<0.01). The IC50 of MCF-7/Adr cells to doxorubicin decreased from (148.2±2.3) nmol/L to (42.9±0.4) nmol/L after pGenesil-siHuR transfection. Compared with untransfected MCF-7/Adr cells, the ratio of cell apoptosis was significantly increased in pGenesil-siHuR transfected MCF-7/Adr cells （\[34.6±1.1\]% vs \[1.1±0.2\]%, P<0.01）after the treatment with doxorubicin. Conclusion: RNA interference of HuR can inhibit the expression of MDR1 gene and increase the sensitivity of multidrug-resistant breast cancer cells to doxorubicin.

国家自然科学基金资助项目（No. 30901788, No. 81272619），山东省自然科学基金资助项目（No. ZR2010HQ038, No. ZR2010HM059）