Inhibition of Tumorigenesis by Intratumoral Delivery of the Circadian Gene mPer2 in C57BL/6 Mice

Cancer Gene Ther. 2007 Sep;14(9):815-8. doi: 10.1038/sj.cgt.7701061. Epub 2007 Jun 22.


Biological clocks are intrinsic time-keeping systems that regulate behavior and physiological functions in most living organisms. Previous works suggested a possible link between the endogenous circadian clock and cell cycle regulation. The mammalian Period-2 gene (mPer2), an important component of the circadian clock mechanism, is recently demonstrated to play an important role in repressing tumor growth. In this study, we found that polyethylenimine-mediated intratumoral Per2 gene delivery had significant antitumor effects in C57BL/6 mice transplanted with Lewis lung carcinoma. Our data illustrated that the Per2 gene delivery inhibited PCNA expression and induced apoptosis. Our results support the emerging role of the circadian clock in critical aspects of tumorigenesis. These findings underscore the potential use of Per2 gene delivery as a novel therapeutic intervention for the treatment of malignant tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Lewis Lung / prevention & control*
  • Cell Cycle Proteins / genetics*
  • Circadian Rhythm / genetics*
  • DNA Primers
  • Immunohistochemistry
  • Injections, Intralesional
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / genetics*
  • Period Circadian Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*


  • Cell Cycle Proteins
  • DNA Primers
  • Nuclear Proteins
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Transcription Factors