Ginkgolic Acid Inhibits Invasion and Migration and TGF--Induced EMT of Lung Cancer Cells Through PI3K/Akt/mTOR Inactivation

被引：211

作者：

Baek, Seung Ho ^{[1
]}

Ko, Jeong-Hyeon ^{[1
]}

Lee, Jong Hyun ^{[1
]}

Kim, Chulwon ^{[1
]}

Lee, Hanwool ^{[1
]}

Nam, Dongwoo ^{[1
]}

Lee, Junhee ^{[1
]}

Lee, Seok-Geun ^{[1
]}

Yang, Woong Mo ^{[1
]}

Um, Jae-Young ^{[1
]}

Sethi, Gautam ^{[2
]}

Ahn, Kwang Seok ^{[1
]}

机构：

[1] Kyung Hee Univ, Coll Korean Med, Seoul, South Korea

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117600, Singapore

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2017年 / 232卷 / 02期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; STAT3 SIGNALING PATHWAY; E-CADHERIN EXPRESSION; CARCINOMA-CELLS; TUMOR PROGRESSION; MULTIPLE-MYELOMA; DENDRITIC CELLS; DOWN-REGULATION; BETA; METASTASIS;

D O I：

10.1002/jcp.25426

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Epithelial-to-mesenchymal transition (EMT) is a critical cellular phenomenon regulating tumor metastases. In the present study, we investigated whether ginkgolic acid can affect EMT in lung cancer cells and the related underlying mechanism(s) of its actions. We found that ginkgolic acid C15:1 (GA C15:1) inhibited cell proliferation, invasion, and migration in both A549 and H1299 lung cancer cells. GA C15:1 also suppressed the expression of EMT related genes (Fibronectin, Vimentin, N-cadherin, MMP-9, MMP-2, Twist and Snail) and suppressed TGF--induced EMT as assessed by reduced expression of mesenchymal markers (Fibronectin, Vimentin, N-cadherin), MMP-9, MMP-2, Twist and Snail. However, GA C15:1 did not affect the expression of various epithelial marker proteins (Occludin and E-cadherin) in both A549 and H1299 cells. TGF--induced morphologic changes from epithelial to mesenchymal cells and induction of invasion and migration were reversed by GA C15:1. Finally, GA C15:1 not only abrogated basal PI3K/Akt/mTOR signaling cascade, but also reduced TGF--induced phosphorylation of PI3K/Akt/mTOR pathway in lung cancer cells. Overall, these findings suggest that GA C15:1 suppresses lung cancer invasion and migration through the inhibition of PI3K/Akt/mTOR signaling pathway and provide a source of potential therapeutic compounds to control the metastatic dissemination of tumor cells. J. Cell. Physiol. 232: 346-354, 2017. (c) 2016 Wiley Periodicals, Inc.

引用

页码：346 / 354

页数：9

共 61 条

[1] Guggulsterone, a farnesoid X receptor antagonist, inhibits constitutive and inducible STAT3 activation through induction of a protein tyrosine phosphatase SHP-1 (Publication with Expression of Concern. See vol. 78, pg. 5184, 2018) [J].