The morbidity and mortality of primary liver cancer is one of the highest amongst all cancers. Deficiency of effective treatment and characteristics of cancer metastasis are believed to be responsible for this situation, thus a great demand is required for new agent development. Polyphyllin II (PP2), an important steroidal saponin extracted from Rhizoma Paris, has emerged as a potential anti-cancer agent, but the effects of PP2 in liver cancers and its underlying mechanisms remain unexplored. In our study, we found that PP2 could remarkably suppress the proliferation of two liver cancer cell lines, HepG2 and BEL7402, resulting in significant cell death. Besides, low doses of PP2 have displayed properties that inhibit cellular motility and invasion of liver cancer cells. In addition, we have found that PP2-mediated cofilin activity suppression was implicated in the inhibition of liver cancer cell motility. Decreased expression of two major hydrolytic enzymes (MMP2/MMP9), through the AKT/NF-κB signaling pathway may also be also responsible for this process. Rescue experiments done with either non-phosphorylatable mutant cofilin-1 (S3A) transfection or an activator of the AKT pathway significantly reversed the inhibition effects of PP2 on liver cancer cells. Taken together, we report a potential agent for liver cancer treatment and reveal its underlying mechanisms.

译文

:原发性肝癌的发病率和死亡率是所有癌症中最高的之一。人们认为有效治疗的缺乏和癌症转移的特征是造成这种情况的原因,因此对新药的开发有很大的需求。 Polyphyllin II(PP2)是从巴黎大根茎中提取的一种重要的甾体皂苷,已成为一种潜在的抗癌剂,但PP2在肝癌中的作用及其潜在机制尚待探索。在我们的研究中,我们发现PP2可以显着抑制两种肝癌细胞系HepG2和BEL7402的增殖,从而导致大量细胞死亡。此外,低剂量的PP2具有抑制细胞运动和侵袭肝癌细胞的特性。另外,我们发现PP2介导的cofilin活性抑制与肝癌细胞运动的抑制有关。通过AKT /NF-κB信号通路减少的两种主要水解酶(MMP2 / MMP9)的表达也可能是这一过程的原因。用不可磷酸化突变体cofilin-1(S3A)转染或AKT途径激活剂进行的抢救实验显着逆转了PP2对肝癌细胞的抑制作用。综上所述,我们报告了一种潜在的肝癌治疗药物,并揭示了其潜在机制。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录