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FB-15 inhibits MGC-803 cells growth by regulating energy metabolism

Xiangping Deng1, Yiyuan Pi2, Zhongli Li3

  • 1Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang City, Hunan Province, PR China; Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang City, Hunan Province, PR China.

Chemico-Biological Interactions
|June 27, 2020
PubMed

Insights

FB-15 demonstrates significant anticancer effects against human gastric carcinoma MGC-803 cells by inhibiting proliferation, inducing apoptosis, and suppressing tumor growth. This compound shows potential as an effective gastric cancer therapeutic, outperforming 5-Fu.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Gastric cancer remains a significant global health challenge with limited effective therapeutic options.
  • Identifying novel anticancer agents with improved efficacy and reduced toxicity is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the anticancer effects of FB-15 on human gastric carcinoma MGC-803 cells in vitro and in vivo.
  • To elucidate the preliminary mechanisms of action, including effects on tubulin and hypoxia-inducible factor 1-alpha (HIF-1α).

Main Methods:

  • In vitro studies involved cell proliferation assays, clone formation assays, cytotoxicity tests on normal gastric cells (GES-1), flow cytometry for apoptosis and cell cycle analysis, and wound healing assays for cell migration.
  • In vivo studies utilized tumor xenograft models in mice.
  • Western blotting and immunohistochemical assays were employed to assess protein expression levels of β3-tubulin and HIF-1α.
  • Molecular docking was used to predict binding modes of FB-15 with tubulin.

Main Results:

  • FB-15 inhibited MGC-803 cell proliferation and clone formation in a concentration- and time-dependent manner.
  • FB-15 induced apoptosis and cell cycle arrest in the S phase in MGC-803 cells, with minimal cytotoxicity to normal GES-1 cells.
  • FB-15 suppressed cell migration and down-regulated the expression of β3-tubulin and HIF-1α.
  • Molecular docking revealed specific binding modes of FB-15 with tubulin.
  • FB-15 significantly suppressed gastric cancer tumor growth in vivo, demonstrating superior efficacy compared to 5-fluorouracil (5-Fu).

Conclusions:

  • FB-15 exhibits potent anticancer activity against human gastric carcinoma MGC-803 cells through multiple mechanisms, including antiproliferation, pro-apoptosis, anti-migration, and modulation of β3-tubulin and HIF-1α.
  • FB-15 demonstrates significant in vivo efficacy in suppressing gastric cancer tumor growth, outperforming the current standard chemotherapy drug 5-Fu.
  • These findings support FB-15 as a promising drug candidate for the development of novel therapeutics for gastric cancer.
Keywords:
AntitumorFB-15HIF-1αMGC-803Tubulin

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