Combined endostatin and TRAIL gene transfer suppresses human hepatocellular carcinoma growth and angiogenesis in nude mice.

Abstract:

:Endostatin can inhibit tumor growth by blocking angiogenesis, whereas tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may function as a soluble cytokine to selectively kill cancer cells without toxicity to most normal cells. To establish the combined anti-tumor therapeutic effect of endostatin and soluble TRAIL (sTRAIL), we performed intra-tumoral human endostatin and sTRAIL gene transfer using plasmid pVAX1 as a vector in a nude mouse model of human liver cancer. For subcutaneously inoculated human BEL7402 cancer, co-expression of both transgenes conferred marked anti-tumor activity with a significant reduction in tumor vessel density and an increase in apoptotic rates, which was accompanied with a strong activation of caspase-3. Importantly, combination therapy employing one-half dose of endostatin and sTRAIL plasmids was more effective than single endostatin or sTRAIL therapy. These results indicate that a pVAX1-mediated combinatorial antiangiogenic and proapoptotic gene therapy approach involving endostatin and sTRAIL can be an effective novel form of treatment for human liver cancer.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Zhang Y,Qu ZH,Cui M,Guo C,Zhang XM,Ma CH,Sun WS

doi

10.4161/cbt.8.5.7687

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

466-73

issue

5

eissn

1538-4047

issn

1555-8576

pii

7687

journal_volume

8

pub_type

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