Autophagy activation contributes to glutathione transferase Mu 1-mediated chemoresistance in hepatocellular carcinoma

Area of Science:

• Molecular Biology
• Oncology
• Biochemistry

Background:

• Glutathione transferase Mu 1 (GSTM1) is implicated in cancer drug resistance through mechanisms like chemotherapeutic hydrolysis or anti-apoptosis pathway activation.
• The specific role of GSTM1 in conferring chemoresistance within hepatocellular carcinoma (HCC) remains largely unelucidated.

Purpose of the Study:

• To investigate the mechanism by which GSTM1 contributes to chemoresistance in hepatocellular carcinoma (HCC).
• To determine the effect of GSTM1 expression levels on the sensitivity of HCC cells to oxaliplatin and sorafenib.
• To explore the potential involvement of autophagy in GSTM1-mediated chemoresistance in HCC.

Main Methods:

• Examined GSTM1 expression in three HCC cell lines with varying metastatic potentials.
• Utilized small interfering RNA (siRNA) to reduce GSTM1 expression in MHCC97-H and Huh-7 cells.
• Assessed cell death using MTT and annexin V/propidium iodide assays.
• Evaluated autophagy activation via GFP-LC3 redistribution and autophagy-related gene 5 (ATG5) expression analysis.

Main Results:

• GSTM1 expression correlated positively with the metastatic potential of HCC cell lines.
• Knockdown of GSTM1 significantly increased oxaliplatin- and sorafenib-induced cell death in HCC cells.
• Inhibition of GSTM1 expression led to a significant reduction in autophagy activation.

Conclusions:

• GSTM1 plays a protective role in HCC cells against oxaliplatin and sorafenib treatment, potentially by activating autophagy.
• Targeting GSTM1 or modulating autophagy presents a potential therapeutic strategy to overcome drug resistance in HCC.
• This study offers a novel perspective on the mechanisms underlying HCC drug resistance.