Pancreatic cancer is among the most aggressive human
cancers, and is resistant to regular
chemotherapy and
radiotherapy. The AT-rich interactive domain containing
protein 1A (ARID1A) gene, a crucial chromatin remodeling gene, mutates frequently in a broad spectrum of
cancers, including
pancreatic cancer. Recent evidence suggests that ARID1A acts as
tumor suppressor and plays an important role in DNA damage repair (DDR). However, the effect of ARID1A on the radiosensitivity of
pancreatic cancer remains unclear. Herein, we investigated the involvement of ARID1A depletion in the radioresistance of
pancreatic cancer cells, and explored the underlying mechanisms. The results reveal that knockdown of ARID1A enhances the radioresistance of
pancreatic cancer cells through suppressing apoptosis, impairing G2-M checkpoint arrest, strengthening DDR, and accompanying activation of PI3K/AKT signaling pathway. Moreover, upon inhibition of PI3K/AKT pathway by PI3K-inhibitor
LY294002 or AKT-inhibitor
mk2206, the radiosensitivity of ARID1A-deficient
pancreatic cancer cells is improved in vitro via increased apoptosis and weakened DDR. Taken together, these data suggest that loss of ARID1A expression enhances radioresistance of
pancreatic cancer through activation of PI3K/AKT pathway, which maybe a promising target for radiosensitization of ARID1A-deficient
pancreatic cancer.