Journal
CANCER GENE THERAPY
Volume 18, Issue 5, Pages 318-325Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2010.81
Keywords
adenovirus; RNA interference; human telomerase RNA; human telomerase reverse transcriptase; combination interference
Categories
Funding
- National Natural Science Foundation of China [30901689]
- Youth Foundation of Sichuan University Chengdu, China [07025]
Ask authors/readers for more resources
Human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) are considered effective molecular targets for current anticancer therapy. In this study, we investigated the therapeutic effects of targeting hTR and hTERT individually or in combination by recombinant adenovirus-delivered small interfering RNA (siRNA) in oral squamous cell carcinoma (OSCC) Tca8113. Further, we screened the optimal strategy for RNA interference. Our results show that these different recombinant adenoviruses specifically reduced the levels of hTR mRNA, hTERT mRNA, hTERT protein and telomerase activity in Tca8113 cells. Moreover, they successfully inhibited xenograft tumor growth in nude mice. The potency of their antitumor activities was ranked as follows: anti-hTR > 4anti-hTR+anti-hTERT > anti-hTERT. Therefore, we demonstrated that the siRNA-expressing recombinant adenoviruses were an effective anticancer tool for treatment of OSCC. Furthermore, the anticancer effect of solely targeting hTR was more direct and efficient, compared with the effect of targeting hTR and hTERT in combination, or hTERT exclusively. The mechanism of this anticancer effect in OSCC was not only related to the inhibition of cell proliferation and the induction of cell apoptosis, but might also involve the inhibition of tumor angiogenesis. Cancer Gene Therapy (2011) 18, 318-325; doi:10.1038/cgt.2010.81; published online 14 January 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available