Anti-proliferative Effects of Protein Arginine Deiminase II inhibition on Retinoblastoma

초록

Purpose : This study investigates the anti-proliferative effects of protein arginine deiminase II (PADI2) on retinoblastoma. Methods : Two retinoblastoma cell lines, Y79 and WERI-Rb1, were treated with BB-Cl-amidine, a chemical inhibitor of PADI2, or with short hairpin RNA (shRNA) targeting PADI2. The effects of inhibition of PADI2 were evaluated through western blotting, cell cycle assay, and cell apoptosis assay. The orthotopic transplantation mouse model was also treated with either a PADI2 inhibitor or shRNA. Results : PADI2 inhibition significantly reduced cancer cell growth via the inactivation of p-AKT and its downstream pathway in retinoblastoma cells. Apoptosis was also induced by increasing the expression of cleaved PARP in Y79 and WERI-Rb1 cells. In vivo experiments in the orthotopic transplantation also showed anti-proliferative effects of PADI2 inhibition. Conclusions : PADI2 inhibition reduced the proliferation of retinoblastoma in vitro and in vivo. We suggest PADI2 inhibition as a novel strategy to treat children with retinoblastoma.