Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University, Chongqing, People's Republic of China.
Pathol Oncol Res. 2010 Sep;16(3):403-11. doi: 10.1007/s12253-009-9227-0. Epub 2009 Dec 3.
Per2 regulates other molecular and biochemical processes beyond their established role in the regulation of the mammalian circadian clock, herein we investigated the growth inhibiting potential of Per2 in human K562 leukemia cells and the underlying mechanisms. The results showed that over-expression of Per2 induced not only cell cycle arrest at G2/M phase but also an increase in apoptosis, which was confirmed by characteristic morphological changes, FCM and evident DNA fragmentation. Further experiments confirmed both up-regulation of P53 and down-regulation of CylinB1and C-myc. On the other hand, while P53 was found to be down-regulated. CylinB1 and C-myc were up-regulated. after Per2 knockdown. In leukemia mice, Per2 transfection was shown to suppress cellular proliferation and accelerate apoptosis of K562 cells. Moreover, fewer leukemia cells were found to have infiltrated into the livers and spleens of the mice from the Per2 transfected group as compared with those from the control group. In summary, Per2 displayed a significant anti-tumor effect through cell cycle arrest and apoptosis induction in K562 cells. These data further support the emerging role of the circadian clock in critical aspects of cancer development and thorough research is underway on the mechanism of Per2 in the leukemia.
Per2 除了在调节哺乳动物生物钟方面的作用外，还调节其他分子和生化过程，在此我们研究了 Per2 在人 K562 白血病细胞中的生长抑制潜力及其潜在机制。结果表明，过表达 Per2 不仅诱导细胞周期在 G2/M 期停滞，还诱导细胞凋亡，这通过特征性形态变化、FCM 和明显的 DNA 片段化得到证实。进一步的实验证实了 P53 的上调和 CylinB1 和 C-myc 的下调。另一方面，虽然发现 P53 下调，但 Per2 敲低后 CylinB1 和 C-myc 上调。在白血病小鼠中，Per2 转染显示抑制 K562 细胞的增殖并加速细胞凋亡。此外，与对照组相比，从 Per2 转染组的小鼠肝脏和脾脏中发现浸润的白血病细胞较少。总之，Per2 通过诱导 K562 细胞周期停滞和凋亡发挥显著的抗肿瘤作用。这些数据进一步支持了生物钟在癌症发展的关键方面的新兴作用，并且正在对 Per2 在白血病中的作用机制进行深入研究。
