Econazole nitrate inhibits PI3K activity and promotes apoptosis in lung cancer cells.
Econazole nitrate inhibits PI3K activity and promotes apoptosis in lung cancer cells.
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DOI：
10.1038/s41598-017-18178-0
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发表时间：
2017-12-21
影响因子：
4.6
通讯作者：
Lin MC
中科院分区：
文献类型：
--
作者：
Dong C;Yang R;Li H;Ke K;Luo C;Yang F;Shi XN;Zhu Y;Liu X;Wong MH;Lin G;Wang X;Leung KS;Kung HF;Chen C;Lin MC
磷脂酰肌醇-3-激酶（PI 3 K）/AKT信号通路在肺癌细胞的增殖、存活和分化等许多细胞过程中起着关键作用。因此，PI 3 K是肺癌治疗的有希望的治疗靶点。在这项研究中，我们应用免费和开源的蛋白质-配体对接软件，筛选了3167个FDA批准的小分子，并鉴定了推定的PI 3 K α抑制剂。其中，抗真菌剂硝酸益康唑在降低病理类型的NSCLC细胞系（包括H661（大细胞肺癌）和A549（腺癌））中的细胞活力方面表现出最高的活性。益康唑可降低p-AKT和Bcl-2蛋白水平，但对ERK磷酸化水平无影响。它以剂量依赖的方式抑制细胞生长并促进凋亡。此外，益康唑和顺铂的组合在H661和A549肺癌细胞系中分别表现出相加和协同作用。最后，我们证明了益康唑显著抑制裸鼠A549肿瘤的生长。我们的研究结果表明，益康唑是一种新的PI 3 K抑制剂，是一种潜在的药物，可用于肺癌治疗单独或与顺铂。
The phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in many cellular processes, including the proliferation, survival and differentiation of lung cancer cells. Thus, PI3K is a promising therapeutic target for lung cancer treatment. In this study, we applied free and open-source protein-ligand docking software, screened 3167 FDA-approved small molecules, and identified putative PI3Kα inhibitors. Among them, econazole nitrate, an antifungal agent, exhibited the highest activity in decreasing cell viability in pathological types of NSCLC cell lines, including H661 (large cell lung cancer) and A549 (adenocarcinoma). Econazole decreased the protein levels of p-AKT and Bcl-2, but had no effect on the phosphorylation level of ERK. It inhibited cell growth and promote apoptosis in a dose-dependent manner. Furthermore, the combination of econazole and cisplatin exhibited additive and synergistic effects in the H661 and A549 lung cancer cell lines, respectively. Finally, we demonstrated that econazole significantly suppressed A549 tumor growth in nude mice. Our findings suggest that econazole is a new PI3K inhibitor and a potential drug that can be used in lung cancer treatment alone or in combination with cisplatin.
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影响因子：
3.7
作者：
Li H;Leung KS;Ballester PJ;Wong MH
通讯作者：
Wong MH
伊曲康唑通过诱导自噬抑制胶质母细胞瘤的生长参与异常胆固醇运输
影响因子：
13.3
作者：
Liu, Rui;Li, Jingyi;Wei, Yuquan
通讯作者：
Wei, Yuquan
影响因子：
5.7
作者：
Maira, Sauveur-Michel;Pecchi, Sabina;Voliva, Charles F.
通讯作者：
Voliva, Charles F.
人类癌症中PIK3CA癌基因的突变。
影响因子：
8.8
作者：
Karakas, B;Bachman, KE;Park, BH
通讯作者：
Park, BH
影响因子：
3.8
作者：
Kim SY;Yoo SJ;Ronnett GV;Kim EK;Moon C
通讯作者：
Moon C