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
  • 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. [email protected].
  • 9. Cancer center, Medical Research Institute, Southwest University, Chongqing, 400716, China. [email protected].
  • 10. Chongqing Engineering and Technology Research Centre for Silk Biomaterials and Regenerative Medicine, Chongqing, 400716, China. [email protected].
  • 11. Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing, 400716, China. [email protected].
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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