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Per2 Inhibits K562 Leukemia Cell Growth In Vitro and In Vivo Through Cell Cycle Arrest and Apoptosis Induction

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Pathology & Oncology Research

Abstract

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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Acknowledgements

We would like to show our thanks to Professor Steven Reppert (University of MassachusettsMedical School, USA) for his offer of the eukaryotic expression vector pcDNA 3.1-Per2; we also extend our thanks to Prof. Tong-chuan He at Chicago Medical Center in America for his kind help in technical expertise and writing instructions. This work was supported by the National Science Foundation of China Grants No.30600748 to Wen-li Feng.

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Authors and Affiliations

  1. Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Cheng-ming Sun, Shi-feng Huang, Jian-ming Zeng, Din-bing Liu, Wen-jun Tian, Xi-dan Zhu & Wen-li Feng

  2. Department of Hematology, clinic college, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Qing Xiao & Zong-gan Huang

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  1. Cheng-ming Sun
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  2. Shi-feng Huang
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  4. Din-bing Liu
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  5. Qing Xiao
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  7. Xi-dan Zhu
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  8. Zong-gan Huang
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  9. Wen-li Feng
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Correspondence to Wen-li Feng.

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Sun, Cm., Huang, Sf., Zeng, Jm. et al. Per2 Inhibits K562 Leukemia Cell Growth In Vitro and In Vivo Through Cell Cycle Arrest and Apoptosis Induction. Pathol. Oncol. Res. 16, 403–411 (2010). https://doi.org/10.1007/s12253-009-9227-0

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  • DOI: https://doi.org/10.1007/s12253-009-9227-0

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