Int J Med Sci 2013; 10(5):634-640. doi:10.7150/ijms.5547
Proliferation Enhanced By NGF-NTRK1 Signaling Makes Pancreatic Cancer Cells More Sensitive To 2DG-Induced Apoptosis
The Department of Surgical Oncology the First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, 277 W. Yanta Road, Xi'an, Shaanxi 710061, China
Cheng Y, Diao Dm, Zhang H, Song YC, Dang CX. Proliferation Enhanced By NGF-NTRK1 Signaling Makes Pancreatic Cancer Cells More Sensitive To 2DG-Induced Apoptosis. Int J Med Sci 2013; 10(5):634-640. doi:10.7150/ijms.5547. Available from http://www.medsci.org/v10p0634.htm
Rapidly proliferating cancer cells rely on increased glucose consumption for survival. The glucose analog 2-deoxy-D-glucose (2DG) cannot complete glycolysis and inhibits the growth of many types of cancers. It is unknown whether reduced glycolysis inhibits the growth of pancreatic cancer. Activation of nerve growth factor (NGF)-neurotrophic tyrosine kinase receptor type 1 (NTRK1) signaling leads to enhanced proliferation of these cells. We investigated the effect of 2DG treatment on the viability of NTRK1-transfected pancreatic cancer cells. After treatment with 2DG, the viability of pancreatic cancer cells was evaluated by MTT assay. SB203580 (a specific inhibitor of the p38-MAPK pathway) and PD98059 (an MAP2K1 [mitogen-activated protein kinase kinase 1, previously, MEK1] inhibitor) were used to inhibit p38-MAPK and ERKs, respectively. The percentage of apoptotic cells was determined by flow cytometry. Overexpression of NTRK1 in pancreatic cancer cells resulted in increased cell proliferation, which was reduced by PD98059-mediated inhibition of ERKs but not by suppression of p38-MAPK with SB203580. After treatment with 2DG, the percentage of apoptotic cells was greater in those with high expression of NTRK1 than in cells with low NTRK1 expression. Blocking the p38-MAPK pathway with SB203580 effectively abolished the apoptosis induced by 2DG. We conclude that pancreatic cancer cells with a high expression of NTRK1 are more sensitive to 2DG-induced apoptosis, through the p38-MAPK pathway.
Keywords: NGF, NTRK1, pancreatic cancer, glycolysis, 2DG