β-carboline derivative Z86 attenuates colorectal cancer cell proliferation and migration by directly targeting PI3K.
β-carboline derivative Z86 attenuates colorectal cancer cell proliferation and migration by directly targeting PI3K.
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DOI：
10.1007/s13659-023-00422-y
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发表时间：
2024-01-03
影响因子：
4.7
通讯作者：
Li, Yan
中科院分区：
文献类型：
--
作者：
Nie, Shiyun;Chang, Lizhong;Huang, Ying;Zhou, Heyang;Yang, Qianqing;Kong, Lingmei;Li, Yan
磷脂酰肌醇3-激酶（PI 3 Ks）是广泛参与细胞增殖、转移和分化的脂质激酶。PI 3 K/Akt/mTOR信号传导的组成性激活在结直肠癌（CRC）中得到充分证实。在这项研究中，我们鉴定了9-乙基-1-（萘-1-基）-9 H-吡啶并[3，4-B]吲哚-3-羧酸异丙酯（Z 86），它是一种新型的PI 3 K α抑制剂，IC 50值为4.28 µM。用DARTS和CETSA试验进一步证实了Z 86与PI 3 K α的结合。免疫荧光分析和Western blotting结果表明，Z 86能有效抑制PI 3 K/AKT信号通路。Z 86通过G 0/G1期阻滞而非凋亡诱导作用显著抑制CRCs的增殖。此外，Z 86还能减轻CRCs的迁移。本研究不仅证实了Z 86是一种新型的PI 3 K α抑制剂，对PI 3 K介导的CRCs生长和迁移具有较强的抑制作用，而且阐明了Z 86抑制Wnt信号通路的分子机制。
Phosphoinositide 3-kinase (PI3Ks) are lipid kinases widely involved in cell proliferation, metastasis and differentiation. Constitutive activation of the PI3K/Akt/mTOR signaling are well confirmed in colorectal cancers (CRCs). In this study, we identified isopropyl 9-ethyl-1-(naphthalen-1-yl)-9 H-pyrido[3,4-b] indole-3-carboxylate (Z86), as a novel PI3Kα inhibitor with the IC50 value of 4.28 µM. The binding of Z86 to PI3Kα was further confirmed with DARTS and CETSA assay. Immunofluorescence analysis and western blotting data demonstrated that Z86 effectively attenuated PI3K/AKT pathway. Z86 caused dramatic proliferation inhibition of CRCs through G0/G1 cycle arrest rather than apoptosis induction. Besides, the migration of CRCs was also relieved by Z86. The present study not only identified Z86 as a novel PI3Kα inhibitor with potent inhibitory efficiency on PI3K-mediated CRCs growth and migration, but also elucidated a reasonable molecular mechanism of Z86 in the Wnt signaling pathway inhibition.
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影响因子：
4.7
作者：
Xu, Hangcheng;Wang, Yan;Han, Yiqun;Wu, Yun;Wang, Jiayu;Xu, Binghe
通讯作者：
Xu, Binghe
EIF4E RNA调节子促进了AKT信号通路。
DOI：
10.1083/jcb.200707018
发表时间：
2008-04-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Culjkovic B;Tan K;Orolicki S;Amri A;Meloche S;Borden KL
通讯作者：
Borden KL
PI3K/Akt/mTOR信号通路及胶质母细胞瘤靶向治疗
影响因子：
--
作者：
Li X;Wu C;Chen N;Gu H;Yen A;Cao L;Wang E;Wang L
通讯作者：
Wang L
影响因子：
4
作者：
Sanchez, Tino W.;Ronzetti, Michael H.;Owens, Ashley E.;Antony, Maria;Voss, Ty;Wallgren, Eric;Talley, Daniel;Balakrishnan, Krishna;Porello, Sebastian E. Leyes;Rai, Ganesha;Marugan, Juan J.;Michael, Samuel G.;Baljinnyam, Bolormaa;Southall, Noel;Simeonov, Anton;Henderson, Mark J.
通讯作者：
Henderson, Mark J.