siRNA-mediated inhibition of hTERT enhances chemosensitivity of hepatocellular carcinoma.
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 could be an effective therapy for HCC.
Guo
Xianling
X
Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
Wang
Weifen
W
Zhou
Feiguo
F
Lu
Zhenghua
Z
Fang
Ruifang
R
Jia
Fengqi
F
Bu
Xinxin
X
Li
Rong
R
Zhang
Baihe
B
Wu
Mengchao
M
Wei
Lixin
L
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D018450:Disease Progression; D020868:Gene Silencing; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*
D034741:RNA, Small Interfering; C509186:TERT protein, human; D019098:Telomerase; D002945:Cisplatin