The clock gene mouse per2 overexpression inhibits growth of human pancreatic cancer cells and shows synergic effect with anti-cancer drug

3325 Circadian rhythms are the dairy oscillations of multiple biological processes, regulated by an endogenous clock. The Period2 gene is essential in controlling circadian rhythm and plays important role in tumor suppression. We examined whether overexpression of the mouse Period2 gene (mPer2) in cultured tumor cells from human tissues inhibits cell growth, using the recombinant adenovirus vector AdmPer2.
 Overexpression of mPer2 in human pancreatic cancer cells (Panc1, Aspc1) reduced cellular proliferation and induced apoptosis. Infection with AdmPer2 also inhibits the cell-cycle progression, inducing cells arrested at G2-M check point. Western blot analyses confirmed these result, showing that infection with AdmPer2 reduced Bcl-XL, Cdc2 and cyclin B1 protein, but increased Bax protein. This synergic effect might be involved with Bcl-XL reduction induced by infection with AdmPer2.
 Moreover, infection with AdmPer2 results to dose-dependent synergic effects with the anticancer agent cisplatin in human pancreatic cancer cells.
 Our results suggest that circadian gene Period2 may play an important role in tumor suppression, not only for mice but also for human. And Period2 gene expression level in circadian oscillations influences the sensitivity to anticancer agent cisplatin.