MSX2 overexpression inhibits gemcitabine-induced caspase-3 activity in pancreatic cancer cells

AIM: To evaluate the effect of MSX2 on gemcitabine-induced caspase-3 activation in pancreatic cancer cell line Panc-1. METHODS: Using V5-tagged MSX2 expression vector, stable transfectant of MSX2 was generated from Panc-1 cells (Px14 cells). Cell viability under gemcitabine administration was determined by MTT assay relative to control cell line (empty-vector transfected Panc-1 cells; P-3EV cells). Hoechst staining was used for the detection of apoptotic cell. Activation of caspase-3 was assessed using Western blotting analysis and direct measurement of caspase-3 specific activities. RESULTS: MSX2 overexpression in Panc-1 cells resulted in decreased gemcitabine-induced caspase-3 activation and increased cell viability under gemcitabine treatment in Px14 cells. CONCLUSION: MSX2 exerts repressive effects on gemcitabine-induced apoptotic pathway. This novel apoptosis-regulating function of MSX2 may provide a new therapeutic target for pancreatic cancer. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.