TGFB1-mediated autophagy facilitates oxaliplatin resistance in stomach adenocarcinoma

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Transforming growth factor beta 1 (TGFB1) is implicated in cancer development.
• The specific role of TGFB1 in stomach adenocarcinoma (STAD) chemotherapy resistance is not well understood.

Purpose of the Study:

• To investigate the mechanism of TGFB1 in mediating resistance to oxaliplatin (OXA) chemotherapy in STAD.
• To identify downstream targets of TGFB1 involved in this process.

Main Methods:

• Analyzed TGFB1 levels in STAD using The Cancer Genome Atlas (TCGA) database.
• Assessed cellular damage, apoptosis, and autophagy via lactate dehydrogenase kit, flow cytometry, and Western blot.
• Utilized LinkedOmics and KEGG for gene correlation analysis.
• Investigated the effect of an autophagy inhibitor (3-methyladenine) and MRAS knockdown.

Main Results:

• TGFB1 expression was elevated in STAD and significantly higher in oxaliplatin-resistant patients.
• TGFB1 reduced cell injury, inhibited apoptosis, and induced autophagy in OXA-resistant STAD cells.
• TGFB1 promotes STAD OXA resistance by upregulating muscle RAS oncogene homolog (MRAS) and inducing autophagy.

Conclusions:

• TGFB1 plays a crucial role in conferring oxaliplatin resistance in stomach adenocarcinoma.
• The TGFB1-MRAS-autophagy axis is a key mechanism driving chemotherapy resistance in STAD.
• Targeting this pathway may represent a novel therapeutic strategy for overcoming STAD chemoresistance.