Tumor cells metastasis as well as proliferation are important factors that can substantially determines the prognosis of cancer. In particular, epithelial–mesenchymal transition (EMT) is key phenomena which can cause tumor cell transition into other organs by promoting the disruption of the cell-cell junctions. Because oxymatrine (OMT) have been reported to attenuate the tumor growth, we investigated whether OMT can down-regulate EMT process in tumor cells. We also focused on transforming growth factor-β (TGF-β)-induced EMT process because EMT process can be significantly induced by this growth factor. The cell viability was measured by MTT and real time cell analysis (RTCA) assay. The expression levels of various proteins involved in the regulation of EMT and Akt/mTOR/PI3K signaling pathway were evaluated by Western blot analysis. mRNA levels of several important EMT markers were analyzed by reverse transcription polymerase chain reaction (RT-PCR). The effects of OMT on the cellular invasion and migration were evaluated by RTCA, wound healing assay, and boyden chamber assays. OMT suppressed the expression of both constitutive and TGF-β-induced mesenchymal markers, such as fibronectin, vimentin, MMP-9, MMP-2, N-cadherin, Twist, and Snail, but induced the levels of epithelial markers. Moreover, OMT down-regulated oncogenic PI3K/Akt/mTOR pathways which lead to a significant attenuation of invasive and migratory potential of lung cancer cells. Overall, our study established a novel anti-metastatic role of OMT against human lung cancer cells.

中文翻译：

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氧化苦参碱作为肺肿瘤细胞上皮间质转化的新型抑制剂的潜在功能


肿瘤细胞的转移和增殖是很大程度上决定癌症预后的重要因素。特别是，上皮-间质转化（EMT）是关键现象，它可以通过促进细胞间连接的破坏而导致肿瘤细胞转化为其他器官。由于氧化苦参碱 (OMT) 已被报道可以减弱肿瘤生长，因此我们研究了 OMT 是否可以下调肿瘤细胞的 EMT 过程。我们还关注转化生长因子-β (TGF-β) 诱导的 EMT 过程，因为这种生长因子可以显着诱导 EMT 过程。通过MTT和实时细胞分析（RTCA）测定来测量细胞活力。通过Western blot分析评估参与EMT和Akt/mTOR/PI3K信号通路调节的各种蛋白的表达水平。通过逆转录聚合酶链式反应 (RT-PCR) 分析了几种重要 EMT 标志物的 mRNA 水平。通过RTCA、伤口愈合试验和博伊登室试验评估OMT对细胞侵袭和迁移的影响。 OMT 抑制组成型和 TGF-β 诱导的间充质标志物的表达，例如纤连蛋白、波形蛋白、MMP-9、MMP-2、N-钙粘蛋白、Twist 和 Snail，但诱导上皮标志物的水平。此外，OMT 下调致癌 PI3K/Akt/mTOR 通路，导致肺癌细胞的侵袭和迁移潜力显着减弱。总体而言，我们的研究确立了 OMT 对人类肺癌细胞的新型抗转移作用。