1. ¹State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Shannxi Province, Xi'an, China
2. ²Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Shannxi Province, Xi'an, China
3. ³Department of Genetics and Development, Fourth Military Medical University, Shannxi Province, Xi'an, China
4. ⁴Department of Immunology, Fourth Military Medical University, Shannxi Province, Xi'an, China

Correspondence: Professor A Yang, Department of Immunology; Fourth Military Medical University; 17 Changle West Road; Xi'an 710032 Shannxi Province, China. E-mail: agyang@fmmu.edu.cn

⁵These authors contributed equally to this work.

Received 9 March 2009; Revised 1 June 2009; Accepted 11 July 2009; Published online 30 October 2009.

Abstract

Abnormal high activation of survivin is involved in carcinogenesis of various types of cancer. Survivin has been shown to promote cell proliferation in human hepatocellular carcinoma (HCC). Survivin-targeting approaches have become a promising strategy for treating HCC. Here, we used a reporter system to screen effective survivin siRNA sequences. The effect of vector-based survivin short hairpin RNA (shRNA) on the malignant phenotype of HCC cells in vitro and in vivo was determined, and an adenovirus-mediated shRNA expression vector was developed to decrease survivin expression of the established HCC tumor in nude mice. In vitro study showed that stable survivin knockdown inhibited cancer cell proliferation, enhanced apoptotic susceptibility, arrested cell cycle in the G1 phase and resulted in apparent mitotic catastrophe. Moreover, cells stably expressing survivin shRNA showed decreased tumorigenicity in nude mice. An additional in vivo study showed that intratumoral injection of adenovirus-delivered survivin shRNA suppressed tumor growth by spontaneous apoptosis of cancer cells and significantly prolonged animal survival. In conclusion, we proved the therapeutic potential of survivin shRNA for the treatment of HCC. And our results indicated that adenovirus-delivered shRNA may serve as a novel therapeutic for HCC.