Effect of PER1, PER3 in cisplatin-treated human gingival cancer cells

Abstract Objectives: PERIOD (PER) are transcriptional regulators that are involved in circadian rhythm, sleep homeostasis, cell proliferation and tumor progression. However, the significance of PER in oral cancer is not well understood. We examined whether PER1 or PER3 are involved in the regulation of apoptosis in human gingival cancer cells. Methods: Cell culture and treatment, RT-PCR and real-time PCR, Short interference RNA (siRNA), Luciferase reporter assay, Western blotting, Immunohistochemistry, Immunofluorescent staining, Cell viability assay. Results: The expression of PER1 was upregulated by Cis-diammine dichloroplatinum (II) (cisplatin: CDDP) treatment in cancer cells, while PER3 was downregulated by CDDP treatment. We also found that siRNA-mediated knockdown of PER1 resulted in enhanced apoptosis compared with the control cells. In addition, PER1 regulated the amount of Bim, an apoptosis-related molecule. On the other hand, PER3 knockdown had the inhibitory effect on apoptosis induced by CDDP treatment. Furthermore, we showed that PER1 was positively stained, by immunohistochemistry, in gingival cancer tissues. Conclusion: These results suggest that PER1 has anti-apoptotic effects in human gingival cancer cells, while PER3 is pro-apoptotic. The balance of PER1 and PER3 may be related to apoptotic reactions in gingival cancer cells.