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Inhibition of β-glucosidase overcomes gastric cancer chemoresistance through inducing lysosomal dysfunction

Zheng Li1, Dongqiang Xu1, Xudong Tong1

  • 1Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Jingzhou Street 39, Xiangyang 441021, China.

Clinics and Research in Hepatology and Gastroenterology
|June 9, 2020
PubMed
Abstract

Insights

Inhibiting beta-glucosidase (GBA1) sensitizes gastric cancer to chemotherapy by restoring lysosomal function and overcoming resistance. This finding highlights GBA1 inhibition as a potential therapeutic strategy for gastric cancer treatment.

Area of Science:

  • Oncology
  • Biochemistry
  • Pharmacology

Background:

  • Gastric cancer presents significant clinical challenges due to poor chemotherapy response.
  • Understanding chemoresistance mechanisms is crucial for developing effective gastric cancer therapies.

Purpose of the Study:

  • To investigate the role of GBA1 in gastric cancer chemoresistance.
  • To explore the therapeutic potential of GBA1 inhibition in overcoming chemotherapy resistance.

Main Methods:

  • Analyzed GBA1 levels in gastric cancer patients and cell lines before and after chemotherapy.
  • Utilized pharmacological and genetic methods to study GBA1 function and downstream effects.
  • Assessed the impact of GBA1 inhibition on gastric cancer cell growth, survival, migration, and chemosensitivity.

Main Results:

  • GBA1 expression and activity were upregulated in gastric cancer cells and patients post-chemotherapy.
  • GBA1 inhibition suppressed gastric cancer growth and enhanced chemotherapy efficacy, particularly in resistant cells.
  • GBA1 inhibition disrupted lysosomal integrity and function in chemoresistant gastric cancer cells.

Conclusions:

  • GBA1 inhibition sensitizes gastric cancer to chemotherapy, demonstrating its therapeutic value.
  • Targeting GBA1 offers a promising strategy for treating gastric cancer, especially in cases of acquired chemoresistance.
Keywords:
ChemoresistanceGBAGastric cancerLysosome functionβ-glucosidase

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