[Anti-hepatocarcinoma effect of recombinant adenovirus carrying melittin gene].

Abstract

OBJECTIVE:

To find a new method of treating hepatocellular carcinoma with melittin by way of using the melittin gene.

METHODS:

The recombinant adenoviruses carrying the melittin gene and alpha-fetoprotein (AFP) promoter (Ad-rAFP-Mel) were constructed through a bacterial homologous recombinant system. The efficiency of the adenovirus mediated gene transfer and the inhibition effect of Ad-rAFP-Mel on the proliferation of hepatocarcinoma cells were determined by X-gal staining and MTT assay respectively. The tumorigenicity of hepatocarcinoma cells transfected by Ad-rAFP-Mel and the antitumor effect of Ad-rAFP-Mel on the transplanted tumors in nude mice were detected in vivo.

RESULTS:

The mRNA of the melittin gene was transcripted in HepG2 hepatocellular carcinoma cells transducted by Ad-rAFP-Mel. The efficiency of adenovirus mediated gene transfered to BEL-7402 hepatocarcinoma cells was 100% when the multiplicities of infection (MOI) of Ad-rAFP-Mel was 10 in vitro and was high in vivo as well. The inhibitive rates of Ad-rAFP-Mel and Ad-rAFP for BEL7402 cells were 66.2%+/-2.7% and 2.9%+/-2.3% (t = 30.83) by MTT assay. The inhibitive rates of Ad-CMV-Mel for BEL7402, SMMC7721 and L02 cells were 58.9%+/-9.6%, 65.9%+/-3.8%, 31.7%+/-1.2%, respectively, and those of the Ad-rAFP-Mel were 6.2%+/-2.7%, 16.1%+/-6.6%, 7.5%+/-3.3%, respectively (t = 1.27; t = 11.31, and t = 12.12, vs. Ad-CMV-Mel group in same cells). The tumorigenicity rates of hepatocarcinoma cells transfected by Ad-rAFP-Mel were decreased. A significant antineoplastic effect was detectd on transplanted tumor in nude mice by intratumoral injection of Ad-rAFP-Mel.

CONCLUSION:

Ad-rAFP-Mel can inhibit specifically the proliferation of AFP-producing human hepatocarcinoma cells in vitro and in vivo. It suggests that animal toxin gene can be used as an interesting antitumor gene.

• Authors: Chang-Quan Ling, Bai Li, Chen Zhang, Wei Gu, Shao-Xiang Li, Xue-Qiang Huang, Ya-Ni Zhang
• Journal: Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology (Zhonghua Gan Zang Bing Za Zhi) Vol. 12 Issue 12 Pg. 741-4 (Dec 2004) ISSN: 1007-3418 [Print] China
• PMID: 15619342 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Fusion Proteins
• alpha-Fetoproteins
• Melitten

Topics

• Adenoviridae (genetics)
• Animals
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Gene Transfer Techniques
• Genetic Therapy (methods)
• Genetic Vectors (genetics)
• Liver Neoplasms, Experimental (pathology)
• Male
• Melitten (biosynthesis, genetics, pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Recombinant Fusion Proteins (biosynthesis, genetics)
• Transcription, Genetic (drug effects)
• alpha-Fetoproteins (biosynthesis, genetics)