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 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.
Mao
Chen-Yu
CY
Department of Oncology Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Hua
Han-Ju
HJ
Chen
Ping
P
Yu
De-Chao
DC
Cao
Jiang
J
Teng
Li-Song
LS
D000256:Adenoviridae; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D050130:Oncolytic Virotherapy; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D000509:alpha-Fetoproteins; D004317:Doxorubicin; D017239:Paclitaxel; D005472:Fluorouracil