Downregulation of GSTM2 enhances gemcitabine chemosensitivity of pancreatic cancer in vitro and in vivo.

Abstract

Glutathione-S-transferases (GSTs) not only show cytoprotective role and their involvement in the development of anticancer drug resistance, but also transmit signals that control cell proliferation and apoptosis. However, the role of GST isoforms in chemotherapy resistance remains elusive in pancreatic cancer. Here, we demonstrated that gemcitabine treatment increased the GSTM2 expression in pancreatic cancer cell lines. Knockdown of GSTM2 by siRNA elevated apoptosis and decreased viability of pancreatic cancer cells treated with gemcitabine. Moreover, in vivo experiments further showed that shRNA induced GSTM2 downregulation enhanced drug sensitivity of gemcitabine in orthotopic pancreatic tumor mice. We also found that GSTM2 levels were lower in tumor tissues than in non-tumor tissues and higher GSTM2 expression was significantly associated with longer overall survival. In conclusion, our findings indicate that GSTM2 expression is essential for the survival of pancreatic cancer cells undergoing gemcitabine treatment and leads to chemo resistance. Downregulation of GSTM2 in pancreatic cancer may benefit gemcitabine treatment. GSTM2 expression in patients also shows significant correlation with overall survival. Thus, our study suggests that GSTM2 is a potential target for chemotherapy optimization and prognostic biomarker of pancreatic cancer.

• Authors: Lisi Peng, Lu Zhuang, Kun Lin, Yao Yao, Yang Zhang, Thiruvengadam Arumugam, Takahiko Fujii, Hui Jiang, Liqi Sun, Zhendong Jin, Zhaoshen Li, Craig Logsdon, Baoan Ji, Haojie Huang
• Journal: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] (Pancreatology) Vol. 21 Issue 1 Pg. 115-123 (Jan 2021) ISSN: 1424-3911 [Electronic] Switzerland
• PMID: 33341341 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• Genetic Markers
• Deoxycytidine
• Glutathione Transferase
• glutathione S-transferase Mu 2
• Gemcitabine

Topics

• Antineoplastic Agents (pharmacology)
• Biomarkers, Tumor
• Deoxycytidine (analogs & derivatives, pharmacology)
• Down-Regulation
• Drug Resistance, Neoplasm (genetics)
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Genetic Markers
• Glutathione Transferase (genetics, metabolism)
• Humans
• Pancreatic Neoplasms (drug therapy)
• RNA Interference
• Gemcitabine