Synergistic antitumor activity of resveratrol and miR-200c in human lung cancer
Synergistic antitumor activity of resveratrol and miR-200c in human lung cancer
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DOI：
10.3892/or.2014.3090
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发表时间：
2014-05-01
期刊：
影响因子：
4.2
通讯作者：
Pei, Ling
中科院分区：
文献类型：
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作者：
Bai, Tao;Dong, Dao-Song;Pei, Ling
MicroRNA已成为一种有前途的分子因子，在癌症诊断和治疗中具有潜在的临床应用。在本研究中，我们使用实时PCR证明肺癌组织中miR-200 c的水平低于正常组织。为了进一步研究肺癌细胞中miR-200 c表达的影响，我们使用转染上调H460细胞中miR-200 c的水平。我们发现，在表达miR-200 c的细胞中，凋亡细胞的百分比高于未转染的细胞。此外，miR-200 c的抗肿瘤活性在体内被证明。值得注意的是，我们证实了reservatol（RESV）在miR-200 c阳性细胞中比在miR-200 c阴性细胞中显示出更强的抗肿瘤活性。最后，我们证明了miR-200 c在H460细胞中的表达通过靶向RECK抑制细胞生长，随后激活JNK信号通路和ER应激。总的来说，这些数据表明miR-200 c表达使H460细胞对RESV敏感，这可能是由于RECK表达。
MicroRNAs have emerged as promising molecular factors with potential for clinical applications in cancer diagnosis and therapy. In the present study, we demonstrated that the level of miR-200c in lung cancer tissues was lower than that in normal tissues using real-time PCR. To further investigate the effects of miR-200c expression in lung cancer cells, we upregulated miR-200c levels in H460 cells using transfection. We found that the percentage of apoptotic cells was higher in the cells expressing miR-200c than that in the untransfected cells. Furthermore, the antitumor activities of miR-200c were demonstrated in vivo. Notably, we confirmed that reservatol (RESV) showed stronger antitumor activities in miR-200c-positive cells than in miR-200c-negative cells. Finally, we demonstrated that expression of miR-200c in H460 cells suppressed cell growth by targeting RECK, followed by activation of the JNK signaling pathway and ER stress. Collectively, these data show that miR-200c expression sensitizes H460 cells to RESV and this is likely due to RECK expression.