siRNA-mediated inhibition of hTERT enhances chemosensitivity of hepatocellular carcinoma

Cancer Biology & Therapy
Xianling GuoLixin Wei

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, there is no effective treatment for HCC. It has been shown that sustained activation of telomerase is essential for the growth and progression of HCC, suggesting that telomerase is a rational target for HCC therapy. Here, we investigated the effects of siRNA-mediated knockdown of hTERT, the catalytic and rate-limiting subunit of telomerase, on the sensitivity of HCC cells to cisplatin. While silencing of hTERT and the resultant inhibition of telomerase activity by infection with the recombinant adenovirus expressing a hTERT siRNA (Ad-si/hTERT) alone did not affect the proliferation and viability of SMMC7721 and HepG2 HCC cells within five days, co-administration of Ad-si/hTERT, but not the empty adenovirus vector, with cisplatin caused much greater extent of apoptosis in vitro under the same conditions and induced significantly more robust inhibition of SMMC7721 and HepG2 tumors growth in a mouse tumor xenograft model than cisplatin monotherapy. Our results demonstrated the synergistic effect between hTERT siRNA and cisplatin in the suppression of HCC progression and indicated that the combination of hTERT-specific siRNA and cisplatin coul...Continue Reading

Citations

Oct 12, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Xian-Ling GuoLi-Xin Wei
Aug 13, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ke YeZhiming Wang
Jan 5, 2013·Mutation Research·Evelyn LamyVolker Mersch-Sundermann
Sep 12, 2013·Journal of Experimental & Clinical Cancer Research : CR·Manale El IdrissiEric Wattel
Mar 5, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Tzu-Yue ShiuTsai-Yuan Hsieh
Jun 23, 2016·Molecular and Clinical Oncology·Masao TakenobuFutoshi Okada

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