A Role for Survivin in Radioresistance of Pancreatic Cancer Cells

Using gene‐transduced pancreatic cancer cells, we examined whether survivin expression is directly involved in regulation of radiosensitivity. Ordinarily radiosensitive MIAPaCa‐2 cells transduced with wild‐type survivin gene (MS cells) proliferated more rapidly than cells transduced with control vector. MS cells were significantly less radiosensitive than control vector‐transduced cells. Radiation‐induced activity of caspase‐3, but not caspase‐7, was significantly inhibited in MS cells. On the other hand, transduction of a dominant‐negative mutant survivin gene into radioresistant PANC‐1 cells augmented radiosensitivity. Further, the radiation‐induced increase in caspase‐3 activity was enhanced, indicating that survivin function was truly inhibited. These results indicate that survivin expression directly down‐regulates radiosensitivity.