MicroRNA-7对非小细胞肺癌表柔比星化疗的增敏作用

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-1mRNA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 mim-ics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-7mimics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。

MicroRNA-7 sensitizes the chemosensitivity of non-small cell lung cancer cells to epirubicin treatment

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.