Combined use of chemotherapeutics and oncolytic adenovirus in treatment of AFP-expressing hepatocellular carcinoma

BACKGROUND:Hepatocellular carcinoma(HCC)which is always refractory to most chemotherapeutic agents may result in poor survival of patients with advanced HCC. Oncolytic adenovirus is a new form for cancer gene therapy via its ability to replicate and kill tumor cells in a tumor-specific manner.In ord...

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Bibliographic Details
Published in:Hepatobiliary & pancreatic diseases international 2009-06, Vol.8 (3), p.282-287
Main Authors: Mao, Chen-Yu, Hua, Han-Ju, Chen, Ping, Yu, De-Chao, Cao, Jiang, Teng, Li-Song
Format: Article
Language:English
Subjects:
Adenoviridae
adenovirus
alpha-Fetoproteins - metabolism
Animals
Antibiotics, Antineoplastic - administration & dosage
Antimetabolites, Antineoplastic - administration & dosage
Antineoplastic Agents - therapeutic use
Antineoplastic Agents, Phytogenic - administration & dosage
carcinoma
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - therapy
Cell Line, Tumor
chemotherapy
Combined Modality Therapy
Doxorubicin - administration & dosage
drug
Drug Therapy, Combination
Fluorouracil - administration & dosage
hepatocellular
Humans
Liver Neoplasms, Experimental - metabolism
Liver Neoplasms, Experimental - therapy
Mice
Mice, Inbred BALB C
oncolytic
Oncolytic Virotherapy
Paclitaxel - administration & dosage
resistance
Treatment Outcome
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Summary:BACKGROUND:Hepatocellular carcinoma(HCC)which is always refractory to most chemotherapeutic agents may result in poor survival of patients with advanced HCC. Oncolytic adenovirus is a new form for cancer gene therapy via its ability to replicate and kill tumor cells in a tumor-specific manner.In order to eradicate tumors effectively, the combination of chemotherapeutic agents and oncolytic adenovirus has been considered.This study aimed to systematically analyze the possibility of synergistic cytotoxicity of oncolytic adenoviruses in combination with chemotherapeutic agents. METHODS:Several types of human HCC cell lines were used to determine the specificity and cytotoxicity of oncolytic adenovirus Ad5-HC and Ad5-AFP(IRES)by measuring cell viability in vitro and antitumor efficiency in vivo.The cytotoxicity of Ad5-HC and Ad5-AFP(IRES) combined with chemotherapeutic agents were also assessed by the methyl thiazolyl tetrazolium assay. RESULTS:Both Ad5-HC and Ad5-AFP(IRES)were significantly cytotoxic to HCC cells with great specificity in vitro and in vivo.The combination of oncolytic adenovirus with 5-FU,doxorubicin,and paclitaxel was synergistically effective for the killing of HCC cells. CONCLUSIONS:These data suggest that oncolytic adenovirus sensitize tumors to chemotherapy and the combination therapy of chemotherapeutic agents and oncolytic adenovirus has an enhanced antitumor effect on HCC cells.
ISSN:1499-3872