Skip Navigation



Carcinogenesis Advance Access published online on October 20, 2009
Carcinogenesis, doi:10.1093/carcin/bgp249
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Han, Z.
Right arrow Articles by Ma, D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Han, Z.
Right arrow Articles by Ma, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A novel oncolytic adenovirus selectively silences the expression of tumor-associated STAT3 and exhibits potent anti-tumoral activity

Zhiqiang Han{dagger}, Zhenya Hong{dagger}, Caihong Chen, Qinglei Gao, Danfeng Luo, Yong Fang, Yang Cao, Tao Zhu, Xuefeng Jiang, Quanfu Ma, Wei Li, Lingfei Han, Daowen Wang, Gang Xu, Shixuan Wang, Li Meng, Jianfeng Zhou* and Ding Ma*

Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China

* To whom correspondence should be addressed. Tel: 86-27-83663351; Fax: 86-27-83662681; Email: dma{at}tjh.tjmu.edu.cn or Tel: 86-27-83662107; Fax: 86-27-83662681; Email: jfzhou{at}tjh.tjmu.edu.cn

Tumor cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance. STAT3 regulates all of these processes in a surprisingly large number of human cancers. Consequently, the STAT3 protein is emerging as an ideal target for cancer therapy. This paper reports the generation of an oncolytic adenovirus (M4), which selectively blocks STAT3 signaling in tumor cells as a novel therapeutic strategy. M4 selectively replicated in tumor cells and expressed high levels of antisense STAT3 cDNA during the late phase of the viral infection in a replication-dependent manner. The viral progeny yield of M4 in tumor cells was much higher than that of the parent adenoviral mutants, Ad5/dE1A. M4 effectively silenced STAT3 and its target genes in tumor cells while sparing normal cells and exhibited potent anti-tumoral efficacy in vitro and in vivo. Systemic administration of M4 significantly inhibited tumor growth in an orthotopic gastric carcinoma mouse model, eliminated abdominal cavity metastases and prolonged survival time. In summary, M4 has low toxicity and great potential as a therapeutic agent for different types of cancers.

{dagger} These authors contributed equally to this work.

Received June 10, 2009; revised September 24, 2009; accepted October 10, 2009.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.