Survivin as a radioresistance factor in pancreatic cancer

We examined whether survivin acts as a constitutive and inducible radioresi stance factor in pancreatic cancer cells. Using a quantitative TaqMan rever se transcription-polymerase chain reaction for survivin mRNA in five pancre atic cancer cell lines, we found an inverse relationship between survivin m RNA expression and radiosensitivity, PANC-1 cells, which had the highest su rvivin mRNA levels, were most resistant to X-irradiation; MIAPaCa-2 cells, which showed the least survivin mRNA expression, were the most sensitive to X-irradiation. Our results suggested that survivin could act as a constitu tive radioresistance factor in pancreatic cancer cells. To determine whethe r radioresistance is enhanced by induction of survivin expression by irradi ation, PANC-1 and MIAPaCa-2 cells were subjected to sublethal doses of X-ir radiation followed by a lethal dose. Survivin mRNA expression was increased significantly in both PANC-1 and MIAPaCa-2 cell lines by pretreatment with a sublethal dose of X-irradiation, as was cell survival after exposure to the lethal dose. In this system, enzymatic caspase-3 activity was significa ntly suppressed in cells with acquired resistance. These results suggest th at survivin also acts as an inducible radioresistance factor in pancreatic cancer cells. Survivin, then, appears to enhance radioresistance in pancrea tic cancer cells; inhibition of survivin mRNA expression may improve the ef fectiveness of radiotherapy.