Molecular insights: Suppression of EGFR and AKT activation by a small molecule in non-small cell lung cancer.
Molecular insights: Suppression of EGFR and AKT activation by a small molecule in non-small cell lung cancer.
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DOI：
10.18632/genesandcancer.154
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发表时间：
2017-09
期刊：
影响因子：
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通讯作者：
Damodaran C
中科院分区：
文献类型：
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作者：
Chandrasekaran B;Tyagi A;Sharma AK;Cai L;Ankem M;Damodaran C
表皮生长因子受体（EGFR）激活事件和哺乳动物雷帕霉素靶点（mTOR）被认为是缓解癌症病情的重要治疗靶点。由于非小细胞肺癌（NSCLC）的生存率较低，目前的治疗模式已转向使用酪氨酸激酶抑制剂（TKI）或间变性淋巴瘤激酶（ALK）抑制剂的个性化治疗策略。在本研究中，我们研究了疣孢菌素J（VJ），一种小分子，在非小细胞肺癌细胞系（H460和A549）的抗癌潜力。该小分子显著抑制两种肺癌细胞系的细胞生长、增殖、集落形成能力，并诱导细胞凋亡。对EGFR（pEGFR-tyr 1173）和AKT（pAKT Serine 473）信号传导的抑制作用下调癌细胞系中的下游促存活信号传导（mTOR和NF-κB）。此外，VJ消除了A549和H460细胞的侵袭和迁移能力。我们还观察到两种细胞系中间充质标志物如N-钙粘蛋白、Slug、β-连环蛋白和波形蛋白表达下调。我们的研究结果表明，VJ抑制癌细胞生长，可能是一种有效的分子，抑制EGFR和AKT信号在NSCLC。
Epidermal growth factor receptor (EGFR) activation events and the mammalian target of rampamycin (mTOR) are considered important therapeutic targets in alleviating cancer conditions. The current treatment paradigm has shifted to personalized treatment strategies with tyrosine kinase inhibitors (TKIs) or anaplastic lymphoma kinase (ALK) inhibitors, due to low survival rates in non-small cell lung cancer (NSCLC) in terms of the prevailing platinum-based therapy. In the present study, we examined the anticancer potential of Verrucarin J (VJ), a small molecule, in NSCLC cell lines (H460 and A549). The small molecule significantly inhibited cell growth, proliferation, colony forming ability, and induced apoptosis in both lung cancer cell lines. The inhibitory effects on EGFR (pEGFR –tyr1173) and AKT (pAKT Serine473) signaling, downregulates downstream pro-survival signaling (mTOR and NF-κB) in cancer cell lines. In addition, VJ abrogated invasive and migratory potential of A549 and H460 cells. We also observed a downregulation of mesenchymal markers such as N-cadherin, Slug, β-catenin, and vimentin expression in both cell lines. Our results suggest that VJ inhibited cancer cell growth and could be a potent molecule to inhibit EGFR and AKT signaling in NSCLC.