期刊
CANCER LETTERS
卷 285, 期 1, 页码 89-98出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.05.006
关键词
Oncolytic adenovirus; Anti-angiogenesis; Canstatin; Gene therapy; Pancreatic cancer
类别
资金
- Project of National Natural Scientific Foundation of China [30600730]
- Major Basic Research Programs of Science and Technology Commission Foundation of Shanghai [03JC14007]
Conditionally-replicating adenovirus (CRAd) therapy is currently being tested against pancreatic cancer and has shown some promise. To improve the efficacy, a novel virus CRAd-Cans was designed by deletion of E1B-55 kDa gene for selective replication in tumor cells, as well as carrying a new angiogenesis inhibitor gene, canstatin. CRAd-Cans mediated higher expression of canstatin in BxPC-3 pancreatic cancer cell line compared to the replication-deficient adenovirus Ad5-Cans. The modified CRAd-Cans manifested the same selective replication and cytocidal effects in pancreatic cancer cells as ONYX-015 in vitro, yet showed greater reduction of tumor growth in nude mice with markedly prolonged survival rate in vivo (P < 0.05), compared to that of either ONYX-015 or Ad5-Cans. Pathological examination revealed viral replication, decreased microvessel density and increased cancer cell apoptosis in CRAd-Cans-treated xenografts. The results suggest that the novel oncolytic virus CRAd-Cans, showing synergistic effects of oncolytic therapy and anti-angiogenesis therapy, is a new promising therapeutics for pancreatic cancer. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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