2. Academic Validation
  3. Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c-Myc axis in gastric cancer

Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c-Myc axis in gastric cancer

  • MedComm (2020). 2021 Jun 3;2(3):467-480. doi: 10.1002/mco2.73.
Yongsen Li 1,  Yongyue Su 2,  Yuzu Zhao 1,  Xiaosong Hu 1,  Gaichao Zhao 1,  Jiang He 1,  Sicheng Wan 1,  Muhan Lü 3,  Hongjuan Cui 1 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Silkworm Genome Biology College of Sericulture Textile and Biomass sciences Southwest University Chongqing China.
  • 2 Department of Orthopaedic 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army Kunming China.
  • 3 Department of Gastroenterology The Affiliated Hospital of Southwest Medical University Luzhou China.
  • 4 Cancer Centre Medical Research Institute Southwest University Chongqing China.
PMID: 34766156 DOI: 10.1002/mco2.73
Abstract

Gastric Cancer (GC) is one of the most familiar malignancy in the digestive system. Demethylzeylasteral (Dem), a natural functional monomer extracted from Tripterygium wilfordii Hook F, shows anti-tumor effects in a variety of cancers, including GC, however, with the underlying mechanism poorly understood. In our study, we show that Dem inhibits the proliferation, migration, and invasion of GC cells, which are mediated by down-regulating c-Myc protein levels. Mechanistically, Dem reduces the stability of c-Myc by up-regulating FBXW7, an E3 ubiquitin Ligase. Moreover, in xenograft tumor model experiment, Dem also inhibits GC, which depends on suppressing c-Myc expression. Finally, Dem enhances GC cell chemosensitivity to the combination treatment of 5-Fluorouracil (5-Fu) and doxorubicin (DOX) in vitro. Together, Dem exerts anti-neoplastic activities through destabilizing and suppressing c-Myc, establishing a theory foundation for using it in future treatment of GC.

Keywords

FBXW7; chemosensitivity; c‐Myc; demethylzeylasteral; gastric cancer.

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