Huang Yan, Wu Sun, Zhang Yuan, Wang Lihua, Guo Yan
Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People's Republic of China.
Onco Targets Ther. 2018 Feb 12;11:769-779. doi: 10.2147/OTT.S149788. eCollection 2018.
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.
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.
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.
In conclusion, TPL exerted anti-tumor effect in T-LBL by inhibiting cell viability, invasion and EMT via regulating the PI3K/AKT/mTOR pathway.
T细胞淋巴母细胞淋巴瘤（T-LBL）是一种在全球广泛传播的疾病。雷公藤甲素（TPL）是从中药中提纯的，具有抗炎、抗生育、抗肿瘤和免疫抑制作用。
在此，进行了体外和体内实验，以研究TPL治疗对T-LBL的抗肿瘤作用及其在T-LBL进展中的潜在机制。
TPL以剂量依赖性方式抑制T-LBL细胞（Jurkat细胞和Molt-3细胞）的增殖。流式细胞术分析表明，TPL处理可提高细胞凋亡率。TPL还上调了Caspase-3、Bax的表达，下调了Bcl-2的表达，表明TPL促进了Jurkat细胞的凋亡。此外，TPL抑制Jurkat细胞的侵袭能力，并以剂量依赖性方式下调MMP-3和MMP-9的表达。TPL处理可降低Snail、Slug、Twist和整合素αVβ6的表达，增加E-钙黏蛋白的表达，表明TPL抑制了Jurkat细胞的上皮-间质转化（EMT）。除此之外，与对照组相比，TPL处理降低了PI3K、Akt和mTOR的磷酸化水平，抑制了AKT激活，提示TPL抑制了T-LBL中的PI3K/Akt/mTOR信号通路。体内实验表明，TPL抑制T-LBL的肿瘤生长并促进肿瘤细胞凋亡。TPL以剂量依赖性方式抑制PCNA、Bcl-2、Snail、p-PI3K、p-Akt和mTOR的表达，提示TPL通过抑制T-LBL中的PI3K/Akt/mTOR信号通路抑制肿瘤生长并促进肿瘤细胞凋亡。
总之，TPL通过调节PI3K/AKT/mTOR通路抑制细胞活力、侵袭和EMT，从而在T-LBL中发挥抗肿瘤作用。
