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

Abstract

Glutathione transferase Mu 1 (GSTM1) induces cancer drug resistance by hydrolyzing cancer chemotherapeutics or activating the anti-apoptosis pathway. However, the chemoresistance-inducing mechanism of GSTM1 in hepatocellular carcinoma (HCC) remains unknown. In the present study, the expression of GSTM1 was examined in three HCC cell lines. Oxaliplatin and sorafenib were selected as chemotherapeutic agents. Small interfering RNA was used to decrease GSTM1 expression. Cell death was measured using MTT and annexin V/propidium iodide assays. Activation of autophagy was evaluated by green fluorescent protein-light chain 3 redistribution and analysis of autophagy-related 5 expression in MHCC97-H and Huh-7 cells. A stepwise increase in GSTM1 expression with increasing metastatic potential of HCC cell lines was revealed. Cell death induced by oxaliplatin and sorafenib was significantly increased following GSTM1-knockdown in MHCC97-H and Huh-7 cells. Activation of autophagy was significantly inhibited by silencing GSTM1 expression. The results of the present study suggest that GSTM1 may protect HCC cells against the effect of oxaliplatin treatment through activating autophagy. The present study provides a novel perspective on HCC drug-resistance.

Screening of molecular targets and construction of a ceRNA network for oxaliplatin resistance in colorectal cancer

“…In this mechanism, oxaliplatin reaches the cytoplasm and forms a hydrate, which reacts with mercapto-containing molecules such as glutathione. 21,22 In recent years, gene engineering technology, such as antisense oligodeoxyribonucleotides (AOD), RNA interference (RNAi) and antisense RNA technology, has been applied to reverse drug resistance in cancer. The molecular targets and pathways that induce oxaliplatin resistance are the prerequisites for the application of genetic engineering technology.…”

Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner

“…6,7 Autophagy is a conserved physiological process that can maintain homeostasis by degrading damaged protein and organelles, which depends on the regulation of autophagy-related protein including microtubule-associated protein light chain 3 (LC3), Beclin 1, and p62. 9 Analogously, targeting endoplasmic reticulum stress-mediated autophagy elevates the effectiveness of sunitinib and gemcitabine on pancreatic cancer. 8,9 In hepatocellular carcinoma, excessive activation of autophagy contributes glutathione transferase Mu 1-mediated resistance to oxaliplatin and sorafenib.…”

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding

“…Interestingly, vitreous seeds result from the clonal selection of RB cells that are able to proliferate in tumor-spheres likewise stem cells, and are prone to develop chemo-resistance properties. Additionally, GSTM1, exclusively detected in RBVS exosomes, has been implicated in cancer chemoresistance [ 105 , 106 ].…”