Combination therapy of androgen-independent prostate cancer using a prostate restricted replicative adenovirus and a replication-defective adenovirus encoding human endostatin-angiostatin fusion gene

Xiong Li, Sudhanshu P. Raikwar, You Hong Liu, Sang Jin Lee, Yan Ping Zhang, Shaobo Zhang, Liang Cheng, Sang Don Lee, Beth Elisa Juliar, Thomas Gardner, Meei Huey Jeng, Chinghai Kao

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15 Citations (Scopus)

Abstract

Although prostate-restricted replicative adenovirus has exhibited significant antitumor efficacy in preclinical studies, it is necessary to develop more potent adenoviruses for prostate cancer gene therapy. We evaluated the synergistic killing effect of prostate-restricted replicative adenovirus and AdEndoAngio, a replication-defective adenovirus expressing the endostatin-angiostatin fusion protein (EndoAngio). When coadministered with AdEndoAngio, prostate-restricted replicative adenovirus significantly elevated EndoAngio expression, suggesting that AdEndoAngio coreplicates with prostate-restricted replicative adenovirus. Conditioned medium from prostate cancer cells infected by prostate-restricted replicative adenovirus plus AdEndoAngio inhibited the growth, tubular network formation, and migration of human umbilical vein endothelial cells better than conditioned medium from prostate cancer cells infected by AdEndoAngio alone. Furthermore, in vivo animal studies showed that the coadministration of prostate-restricted replicative adenovirus plus AdEndoAngio resulted in the complete regression of seven out of eight treated androgen-independent CWR22rv tumors, with a tumor nodule maintaining a small size for 14 weeks. The residual single tumor exhibited extreme pathologic features together with more endostatin-reactive antibody-labeled tumor cells and fewer CD31-reactive antibody-labeled capillaries than the AdEndoAngio-treated tumors. These results show that combination therapy using prostate-restricted replicative adenovirus together with antiangiogenic therapy has more potent antitumor effects and advantages than single prostate-restricted replicative adenovirus and deserves more extensive investigation.

Original languageEnglish
Pages (from-to)676-684
Number of pages9
JournalMolecular Cancer Therapeutics
Volume5
Issue number3
DOIs
StatePublished - Mar 2006

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Angiostatins
Endostatins
Human Adenoviruses
Gene Fusion
Adenoviridae
Androgens
Prostate
Prostatic Neoplasms
Therapeutics
Conditioned Culture Medium
Neoplasm Antibodies
Neoplasms
Neoplasm Genes
Human Umbilical Vein Endothelial Cells
Residual Neoplasm
Genetic Therapy
Proteins

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Combination therapy of androgen-independent prostate cancer using a prostate restricted replicative adenovirus and a replication-defective adenovirus encoding human endostatin-angiostatin fusion gene. / Li, Xiong; Raikwar, Sudhanshu P.; Liu, You Hong; Lee, Sang Jin; Zhang, Yan Ping; Zhang, Shaobo; Cheng, Liang; Lee, Sang Don; Juliar, Beth Elisa; Gardner, Thomas; Jeng, Meei Huey; Kao, Chinghai.

In: Molecular Cancer Therapeutics, Vol. 5, No. 3, 03.2006, p. 676-684.

Research output: Contribution to journalArticle

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