2. Academic Validation
  3. Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric cancer

Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric cancer

  • J Exp Clin Cancer Res. 2020 Oct 30;39(1):230. doi: 10.1186/s13046-020-01743-3.
Chongyang Li 1 2 3 4,  Chaowei Deng 1 2 3 4,  Guangzhao Pan 1 2 3 4,  Xue Wang 5,  Kui Zhang 1 2 3 4,  Zhen Dong 1 2 3 4,  Gaichao Zhao 1 2 3 4,  Mengqin Tan 1 2 3 4,  Xiaosong Hu 1 2 3 4,  Shaomin Shi 6 7,  Juan Du 7,  Haoyan Ji 1 2 3 4,  Xiaowen Wang 1 2 3 4,  Liqun Yang 1 2 3 4,  Hongjuan Cui 8 9 10 11
Affiliations

Affiliations

  • 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.
  • 3 Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China.
  • 4 Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China.
  • 5 Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400014, China.
  • 6 The Fifth Hospital of Shijiazhuang, Shijiazhuang, 050021, China.
  • 7 The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.
  • 8 State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, #1, Tiansheng Rd., Beibei District, Chongqing, 400716, China. hcui@swu.edu.cn.
  • 9 Cancer center, Medical Research Institute, Southwest University, Chongqing, 400716, China. hcui@swu.edu.cn.
  • 10 Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China. hcui@swu.edu.cn.
  • 11 Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China. hcui@swu.edu.cn.
PMID: 33126914 DOI: 10.1186/s13046-020-01743-3
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

Apoptosis; Cell cycle; Drug-resistance; FBXW7; Gastric cancer; Lycorine hydrochloride; MCL1; PDX model.

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