Liver Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 21, 2006; 12(47): 7613-7620
Published online Dec 21, 2006. doi: 10.3748/wjg.v12.i47.7613
Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic adenovirus in human hepatocellular carcinoma
Chang-Qing Su, Xing-Hua Wang, Jie Chen, Yong-Jing Liu, Wei-Guo Wang, Lin-Fang Li, Meng-Chao Wu, Qi-Jun Qian
Chang-Qing Su, Yong-Jing Liu, Wei-Guo Wang, Lin-Fang Li, Meng-Chao Wu, Qi-Jun Qian, Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
Qi-Jun Qian, Xinyuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
Xing-Hua Wang, Jie Chen, Changhai Hospital, Second Military Medical University, Shanghai 200438, China
Chang-Qing Su, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Life Science College, Nanjing Normal University, Nanjing 210097, Jiangsu Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Natural Science Foundation of China, No. 30572149; the National 863 High Technology R&D Project of China, No. 2003AA216030
Correspondence to: Qi-Jun Qian, Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Rd., Shanghai 200438, China. qianqj@sino-gene.cn
Telephone: +86-21-25070836 Fax: +86-21-35030677
Received: August 9, 2006
Revised: November 12, 2006
Accepted: November 20, 2006
Published online: December 21, 2006
Abstract

AIM: To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT).

METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and

in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice.

RESULTS: SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells.

CONCLUSION: hTERT promoter-regulated replicative adenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.

Keywords: Virotherapy; Oncolytic adenovirus; Human telomerase reverse transcriptase; Hepatocellular carcinoma; Animal tumor model