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

Cheng-ming Sun; Shi-feng Huang; Jian-ming Zeng; Din-bing Liu; Qing Xiao; Wen-jun Tian; Xi-dan Zhu; Zong-gan Huang; Wen-li Feng

doi:10.1007/s12253-009-9227-0

Pathology & Oncology Research

September 2010, Volume 16, Issue 3, pp 403–411

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

Authors
Authors and affiliations

Cheng-ming Sun
Shi-feng Huang
Jian-ming Zeng
Din-bing Liu
Qing Xiao
Wen-jun Tian
Xi-dan Zhu
Zong-gan Huang
Wen-li FengEmail author

Article

First Online:: 03 December 2009

Received:: 07 May 2009
Accepted:: 09 November 2009

DOI: 10.1007/s12253-009-9227-0

Cite this article as:: Sun, C., Huang, S., Zeng, J. et al. Pathol. Oncol. Res. (2010) 16: 403. doi:10.1007/s12253-009-9227-0

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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.

Keywords

Circadian clock Per2 Apoptosis Cell cycle arrest K562 cell

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Authors and Affiliations

Cheng-ming Sun
- 1
Shi-feng Huang
- 1
Jian-ming Zeng
- 1
Din-bing Liu
- 1
Qing Xiao
- 2
Wen-jun Tian
- 1
Xi-dan Zhu
- 1
Zong-gan Huang
- 2
Wen-li Feng
- 1
Email author

1.Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics, Ministry of EducationChongqing Medical UniversityChongqingPeople’s Republic of China
2.Department of Hematology, clinic collegeChongqing Medical UniversityChongqingPeople’s Republic of China

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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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