Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric ca
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(2020) 39:230
RESEARCH
Open Access
Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric cancer Chongyang Li1,2,3,4†, Chaowei Deng1,2,3,4†, Guangzhao Pan1,2,3,4, Xue Wang5, Kui Zhang1,2,3,4, Zhen Dong1,2,3,4, Gaichao Zhao1,2,3,4, Mengqin Tan1,2,3,4, Xiaosong Hu1,2,3,4, Shaomin Shi6,7, Juan Du7, Haoyan Ji1,2,3,4, Xiaowen Wang1,2,3,4, Liqun Yang1,2,3,4 and Hongjuan Cui1,2,3,4*
Abstract Background: Lycorine hydrochloride (LH), an alkaloid extracted from the bulb of the Lycoris radiata, is considered to have anti-viral, anti-malarial, and anti-tumorous effects. At present, the underlying mechanisms of LH in gastric cancer remain unclear. MCL1, an anti-apoptotic protein of BCL2 family, is closely related to drug resistance of tumor. Therefore, MCL1 is considered as a potential target for cancer treatment. Methods: The effect of LH on gastric cancer was assessed in vitro (by MTT, BrdU, western blotting…) and in vivo (by immunohistochemistry). Results: In this study, we showed that LH has an anti-tumorous effect by down-regulating MCL1 in gastric cancer. Besides, we unveiled that LH reduced the protein stability of MCL1 by up-regulating ubiquitin E3 ligase FBXW7, arrested cell cycle at S phase and triggered apoptosis of gastric cancer cells. Meanwhile, we also demonstrated that LH could induce apoptosis of the BCL2-drug-resistant-cell-lines. Moreover, PDX (Patient-Derived tumor xenograft) model experiment proved that LH combined with HA14–1 (inhibitor of BCL2), had a more significant therapeutic effect on gastric cancer. Conclusions: The efficacy showed in our data suggests that lycorine hydrochloride is a promising anti-tumor compound for gastric cancer. Keywords: Gastric cancer, Lycorine hydrochloride, MCL1, FBXW7, Apoptosis, Cell cycle, Drug-resistance, PDX model
* Correspondence: [email protected]; [email protected] † Chongyang Li and Chaowei Deng contributed equally to this work. 1 State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, #1, Tiansheng Rd., Beibei District, Chongqing 400716, China 2 Cancer center, Medical Research Institute, Southwest University, Chongqing 400716, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly fro
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