已发表论文

雷公藤内酯醇通过调节 PI3K/AKT/mTOR 信号通路抑制细胞活力、侵袭和上皮 - 间充质转化,从而在T细胞淋巴母细胞性淋巴瘤中发挥抗肿瘤作用

 

Authors Huang Y, Wu S, Zhang Y, Wang L, Guo Y

Received 23 August 2017

Accepted for publication 19 October 2017

Published 12 February 2018 Volume 2018:11 Pages 769—779

DOI https://doi.org/10.2147/OTT.S149788

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Tohru Yamada

Introduction: T-cell lymphoblastic lymphoma (T-LBL) is a widely disseminated disease worldwide. Triptolide (TPL) is purified from Chinese herb and displays anti-inflammatory, anti-fertility, anti-tumor and immunosuppressive effects. 
Materials and methods: Here, in vitro and in vivo experiments were conducted to investigate the anti-tumor effect of TPL treatment in T-LBL and the potential mechanism in T-LBL progression. 
Results: TPL inhibited cell proliferation of T-LBL cells (Jurkat cells and Molt-3 cells) in a dose-dependent manner. Flow cytometry analysis showed that cell apoptosis rate was increased by TPL treatment. TPL also up-regulated the expression of Caspase-3, Bax and down-regulated the expression of Bcl-2, indicating that TPL promoted apoptosis in Jurkat cells. Moreover, TPL inhibited invasion ability of Jurkat cells and down-regulated the expression of MMP-3 and MMP-9 in a dose-dependent manner. The expression of Snail, Slug, Twist and Integrin αVβ6 was decreased and the expression of E-cadherin was increased by TPL treatment, indicating that TPL inhibited EMT of Jurkat cells. Apart from that, TPL treatment attenuated the phoslevels of PI3K, Akt and mTOR and suppressed AKT activation compared with control group, suggesting that TPL inhibited PI3K/Akt/mTOR signal pathway in T-LBL. In vivo experiments showed that TPL inhibited tumor growth of T-LBL and promoted apoptosis of tumor cells. The expression of PCNA, Bcl-2, Snail, p-PI3K, p-Akt and mTOR was suppressed by TPL in a dose-dependent manner, suggesting that TPL suppressed tumor growth and promoted apoptosis of tumor cells by inhibiting PI3K/Akt/mTOR signal pathway in T-LBL. 
Conclusion: In conclusion, TPL exerted anti-tumor effect in T-LBL by inhibiting cell viability, invasion and EMT via regulating the PI3K/AKT/mTOR pathway.
Keywords: triptolide, T-cell lymphoblastic lymphoma, invasion, EMT, PI3K/AKT/mTOR