1. ¹Laboratory for Cellular and Molecular Immunology, Shanghai Cancer Institute, Shanghai, China
2. ²Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
3. ³Xinyuan Institute of Medicine and Biotechnology, School of Life Science, Zhejiang Sci-Tech University, Hangzhou, China

Correspondence: Professor X Zhao, Laboratory for Cellular and Molecular Immunology, Shanghai Cancer Institute, Ln2200/25 Xie Tu Road, Shanghai 200032, China. E-mail: xtzhao@sci.shmu.edu.cn; Professor XY Liu, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academyof Sciences, 320 YueYang Road, Shanghai 200031, China. E-mail: xyliu@sibs.ac.cn

⁴These authors contributed equally to this work.

Received 7 January 2008; Revised 22 April 2008; Accepted 3 June 2008; Published online 11 July 2008.

Abstract

We had characterized earlier the novel tumor suppressor gene hepatocellular carcinoma suppressor 1 (HCCS1), and demonstrated that expression of exogenous HCCS1 gene in human hepatocarcinoma cells could remarkably suppress their abilities to develop tumors in nude mice and to form colonies in soft agar. In this study, we provide further experimental evidence to confirm the role of HCCS1 as a tumor suppressor gene and investigate its potential in therapeutic applications by using adenovirus vectors. We show that HCCS1 overexpression, mediated by replication-deficient adenovirus, significantly suppressed the growth of human colorectal cancer cells, as well as hepatocellular carcinoma cells in vitro and in vivo. To further improve its antitumor efficacy, we inserted the HCCS1 gene into an oncolytic adenovirus. This HCCS1-armed oncolytic adenovirus exhibited a dramatic inhibitory effect on cancer cells in vitro and in vivo, and led to a complete regression of 50% of established tumor xenografts in nude mice. Taken together, our data suggest that HCCS1 is a promising therapeutic gene for the treatment of human cancers.