Triple-controlled oncolytic adenovirus expressing melittin to exert inhibitory efficacy on hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a highly malignant disease, and its outcome of routine therapies is poor. Comprehensive treatment including gene therapy is an important way to improve patients' prognosis and survival. In this study, we successfully constructed a triple-controlled cancer-selec...

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Bibliographic Details
Published in:International journal of clinical and experimental pathology 2015-01, Vol.8 (9), p.10403-10411
Main Authors: Qian, Chun-Yu, Wang, Kai-Li, Fang, Fan-Fu, Gu, Wei, Huang, Feng, Wang, Fu-Zhe, Li, Bai, Wang, Li-Na
Format: Article
Language:English
Subjects:
Adenoviridae
Animals
Antineoplastic Agents - pharmacology
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell Proliferation - drug effects
Genetic Therapy - methods
Humans
Liver Neoplasms - pathology
Male
Melitten - administration & dosage
Melitten - genetics
Mice, Inbred BALB C
Mice, Nude
Oncolytic Virotherapy - methods
Original
Xenograft Model Antitumor Assays
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Summary:Hepatocellular carcinoma (HCC) is a highly malignant disease, and its outcome of routine therapies is poor. Comprehensive treatment including gene therapy is an important way to improve patients' prognosis and survival. In this study, we successfully constructed a triple-controlled cancer-selective oncolytic adenovirus, QG511-HA-Melittin, carrying melittin gene, in which the hybrid promoter, hypoxia-response element (HRE)-AFP promoter, was used to control viral E1a expression targeting AFP-positive cancer cells in hypoxia microenviroment, and the E1b-55 kDa gene was deleted in cancer cells with p53-deficiency. The cytological experiments found that the viral replication of QG511-HA-Melittin was increased to 12800-folds in Hep3B cells within 48 h, and 130-folds in SMMC-7721, but the virus did not replicate in L-02 cells. QG511-HA-Melittin had a strong inhibition effect on AFP-positive HCC cell proliferation, such as Hep3B and HepG2, whereas, there was low or no inhibition effect of QG511-HA-Melittin on AFP-negative cancer cells SMMC-7721 and normal cells L-02. In the in vivo experiment, compared with the blank control group, QG511-HA-Melittin can significantly inhibit the growth of HCC xenografts (P
ISSN:1936-2625