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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