In Vitro And In Vivo Study Of The Tumor Suppressive Effects Of Circadian Gene Period2

Cancer is one kind of major diseases that threaten people's health. Cancer incidence ranks the 2nd of ten major diseases. Although much advance has been achieved for the diagnosis and treatment of cancer, the long-term outcome for many cancer patients is still poor. Studies of animal models and human tumor samples have revealed that the disruption of circadian rhythms is an important endogenous factor that contributes to mammalian cancer development. The present study was designed to investigate the role of one key clock protein, PER2, in cancer progression. We studied the impact of PER2 overexpression and downregulation on Lewis lung cancer (LLC) and mouse mammary carcinoma cell EMT6 cell growth and apoptosis.Per2 gene, an indispensable component of the circadian clock, not only modulates circadian oscillations, but also regulates organic function. We examined whether the overexpression of Per2 gene in tumor cells may influence cell growth and induce apoptosis. The eukaryotic expression vector pcDNA3.1(+)-mPer2 was transfected into LLC cells, EMT6 cells, and NIH3T3 cells. The effect of mPer2 overexpression on cell proliferation was analyzed by MTT assay and colony formation assay. The effects of mPer2 on apoptosis was also investigated using multiple methodology, including flow cytometry, DNA fragmentation, Hoechst 33342 staining, and electron microscopy. Overexpression of the mouse mPer2 in LLC cells and EMT6 cells results in reduced cellular proliferation and rapid apoptosis, but not in NIH 3T3 cells. Cell cycle analysis indicated that mPer2 overexpression resulted in G1 arrest in both LLC and EMT6...