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.

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High levels of visfatin are correlated with worse clinical prognosis of various cancers. Still, the effects and mechanisms of visfatin on progression of non-small cell lung cancer (NSCLC) remain unclear. This study revealed that plasma levels of visfatin in patients with NSCLC (585 ± 287 pg/ml) were significantly (p < 0.01) higher than those in healthy people (142 ± 61.1 pg/ml). The high level of plasma visfatin was found to be significantly (p < 0.05) correlated with TNM stage, lymph node metastasis and distant metastasis. Visfatin treatment can increase the migration and invasion of NSCLC cells via up-regulation of metalloproteinase-2 (MMP-2) and MMP-9. Both si-MMP-2 and si-MMP-9 attenuated visfatin-induced migration of NSCLC cells. The inhibitor of NF-κB, while not ERK1/2, p38-MAPK or PI3K/Akt, can significantly abolish visfatin-induced migration of A549 cells and up-regulation of MMP-2 and MMP-9. Furthermore, visfatin can increase the phosphorylation of IκBα and p65 and the transcription activities of NF-κB in NSCLC cells. ACHP, the inhibitor of IKK-β, blocked visfatin-induced activation of p65 and up-regulation of MMP-2 and MMP-9. Collectively, our data revealed that visfatin can trigger the in vitro migration and invasion of NSCLC cells via up-regulation of MMPs through activation of NF-κB.