Bai Can, Zhang Zhe, Zhou Li, Zhang Huan-Yu, Chen Yan, Tang Yong
Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
Front Pharmacol. 2020 Sep 18;11:576547. doi: 10.3389/fphar.2020.576547. eCollection 2020.
Effective chemotherapy drugs for colorectal cancer remain a challenge. In this research, Ziyuglycoside II (Ziyu II), exhibits considerable antitumor activity against CRC cells both and . The results showed that Ziyu II induced apoptosis through the accumulation of reactive oxygen species (ROS), which was necessary for Ziyu II to inhibit colorectal cancer cells. Intriguingly, The treatment of Ziyu II triggered complete autophagic flux in CRC cells. Inhibition of autophagy partially reversed Ziyu II-induced growth inhibition, demonstrating a cytotoxic role of autophagy in response to Ziyu II-treated. Mechanism indicated that Ziyu II-induced autophagy by inhibiting Akt/mTOR pathway. Akt reactivation partially reduced Ziyu II-induced LC3-II turnover and LC3 puncta accumulation. Especially, Ziyu II improves the sensitivity of 5-fluorouracil which is the first-line chemotherapy drug in colorectal cancer cells. This research provides novel insight into the molecular mechanism of Ziyu II's anti-proliferation, including apoptosis and autophagy, and lays a foundation for the potential application of Ziyu II in clinical CRC treatment.
有效的结直肠癌化疗药物仍然是一个挑战。在本研究中，紫榆苷II（Ziyu II）对结直肠癌细胞显示出相当大的抗肿瘤活性。结果表明，Ziyu II通过活性氧（ROS）的积累诱导细胞凋亡，这是Ziyu II抑制结直肠癌细胞所必需的。有趣的是，Ziyu II处理引发了结直肠癌细胞中完全的自噬流。自噬的抑制部分逆转了Ziyu II诱导的生长抑制，表明自噬在响应Ziyu II处理时具有细胞毒性作用。机制表明，Ziyu II通过抑制Akt/mTOR途径诱导自噬。Akt的重新激活部分降低了Ziyu II诱导的LC3-II周转和LC3斑点积累。特别是，Ziyu II提高了5-氟尿嘧啶（结直肠癌一线化疗药物）在结直肠癌细胞中的敏感性。本研究为Ziyu II抗增殖的分子机制提供了新的见解，包括细胞凋亡和自噬，并为Ziyu II在临床结直肠癌治疗中的潜在应用奠定了基础。
