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


CONCLUSIONS
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.
Hamada
Shin
S
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aobaku, Sendai city, Miyagi 980-8574, Japan.
Satoh
Kennichi
K
Kimura
Kenji
K
Kanno
Atsushi
A
Masamune
Atsushi
A
Shimosegawa
Tooru
T
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C084119:MSX2 protein; D003841:Deoxycytidine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000093542:Gemcitabine