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灯盏花素通过增强微小RNA-7的表达来抑制非小细胞肺癌的生长。

Breviscapine suppresses the growth of non-small cell lung cancer by enhancing microRNA-7 expression.

作者信息

Zeng Jian, Cai Shunv

机构信息

Department of Thoracic Tumor Surgery, Zhejiang Cancer Hospital, Hangzhou 310004, China.

出版信息

J Biosci. 2017 Mar;42(1):121-129. doi: 10.1007/s12038-017-9670-0.

Abstract

Breviscapine (BVP) has previously been shown to inhibit the proliferation of hepatocellular carcinoma cells. However, little is known about the effects of BVP on non-small cell lung cancer (NSCLC) growth. Here, we aimed to study the effects of BVP on human NSCLC growth. We employed A549, NCL-H460 and A549 cells transfected with microRNA-7 (miR-7) mimic and inhibitor to investigate the effect of BVP on cell proliferation, apoptosis and apoptosis-associated molecules. The results showed that BVP significantly reduced the growth of A549 and NCLH460 cells in a concentration-dependent and time-dependent manner, accompanied by a significant elevation of apoptosis. Additionally, the present study also confirmed that BVP-treated A549 cells showed increased levels of Bax and microRNA-7 (miR-7) and a decreased level of Bcl-2. The up-regulation of miR-7 enhanced the BVP sensitivity of NSCLC cells by suppressing cell proliferation and promoting cell apoptosis, while the inhibition of miR-7 reversed the anti-proliferative pro-apoptotic effects of BVP. Pre-treatment with miR-7 mimics enhanced the BVP-mediated down-regulation of Bax/Bcl-2 in NSCLC cells, while pre-treatment with the miR-7 inhibitor blocked the BVPmediated down-regulation of Bax/Bcl. Taken together, these results confirm that BVP effectively inhibits NSCLC proliferation and that miR-7, as a novel target, is likely involved in BVP-induced growth suppression and the apoptosis of NSCLC cells.

摘要

灯盏花素(BVP)先前已被证明可抑制肝癌细胞的增殖。然而,关于BVP对非小细胞肺癌(NSCLC)生长的影响知之甚少。在此,我们旨在研究BVP对人NSCLC生长的影响。我们使用转染了微小RNA-7(miR-7)模拟物和抑制剂的A549、NCL-H460和A549细胞来研究BVP对细胞增殖、凋亡及凋亡相关分子的影响。结果表明,BVP以浓度和时间依赖性方式显著降低A549和NCLH460细胞的生长,并伴有凋亡的显著增加。此外,本研究还证实,经BVP处理的A549细胞中Bax和微小RNA-7(miR-7)水平升高,Bcl-2水平降低。miR-7的上调通过抑制细胞增殖和促进细胞凋亡增强了NSCLC细胞对BVP的敏感性,而miR-7的抑制则逆转了BVP的抗增殖促凋亡作用。用miR-7模拟物预处理增强了BVP介导的NSCLC细胞中Bax/Bcl-2的下调,而用miR-7抑制剂预处理则阻断了BVP介导的Bax/Bcl的下调。综上所述,这些结果证实BVP有效抑制NSCLC增殖,并且miR-7作为一个新靶点,可能参与了BVP诱导的生长抑制和NSCLC细胞的凋亡。

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