目的：研究microRNA-7（miR-7）对非小细胞肺癌A549和H1299细胞表柔比星（epirubicin，EPI）化疗的增敏作用及其机制。方法：EPI、miR-7 mimics单独或联合处理A549和H1299细胞后，CCK-8法检测A549和H1299细胞的增殖，Annexin-V/PI染色流式细胞术检测A549和H1299细胞的凋亡，实时定量PCR检测A549和H1299细胞中EGFR及Raf-1 mRNA的表达。结果：单独使用EPI或转染miR-7 mimics均可抑制A549和H1299细胞的增殖（P<0.05），而转染miR-7 mimics后再以50～400 ng/ml EPI处理，较单独EPI处理显著增强对A549和H1299细胞增殖的抑制作用（P<0.05）。当miR-7 mimics与EPI联用时，A549和H1299细胞的凋亡率则分别较EPI单独处理组增加（54.9±0.4）%和（67.2±0.5）%（均P<001），且伴随EGFR及Raf-1 mRNA表达量的显著下降（P<0.01），A549细胞中分别降低（68.0±6.0）%和（78.2±3.9）%，H1299细胞中分别降低（94.8±6.2）%和（87.8±4.3）%。结论：miR-7可通过下调EGFR及Raf-1 mRNA的表达，协同EPI抑制非小细胞肺癌A549和H1299细胞的增殖，并促进细胞凋亡。

Objective:To investigate the effect of microRNA-7 (miR-7) on the chemosensitivity of non-small cell lung cancer A549 and H1299 cells to epirubicin (EPI) treatment and its molecular mechanism. Methods: After being treated with EPI and transfected with miR-7 mimics alone or in combination, the cell proliferation of A549 and H1299 cells was measured by CCK-8; the cell apoptosis was detected by Annexin V/PI staining; and the expressions of EGFR and Raf-1 mRNA were examined by real-time PCR. Results: Both EPI treatment and miR-7 mimics transfection inhibited the proliferation of A549 and H1299 cells (P<0.05), while EPI (50-400 ng/ml) combined with miR-7 mimics had a stronger inhibitory effect on the proliferation of A549 and H1299 cells than EPI treatment alone (P<0.05). The percentages of apoptotic cells was significantly increased in the combination treatment group by (54.9±0.4)% in A549 cells and (672±0.5)% in H1299 cells (P<0.01) compared with that of the EPI treatment group, and the expressions of EGFR and Raf-1 mRNA were also downregulated by (68.0±6.0)% and (78.2±3.9)% in A549 cells, (94.8±6.2)% and (87.8±4.3)% in H1299 cells after the combination treatment of miR-7 mimics and EPI compared with that of the EPI treatment alone group (P<0.01).Conclusion: miR-7 enhances the inhibitory and pro-apoptosis effect of EPI on A549 and H1299 cells through the downregulation of EGFR and Raf-1 mRNA.

国家自然科学基金资助项目（No. 81072408）；上海市科委基金资助项目（No. 10JC1401100）