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

作　　者：Mao, Chen-Yu Hua, Han-Ju Chen, Ping Yu, De-Chao Cao, Jiang Teng, Li-Song 

机构地区：[1]Zhejiang Univ, Sch Med, Dept Surg Oncol, Affiliated Hosp 1, Hangzhou 310003, Peoples R China [2]Zhejiang Univ, Sch Med, Sir Run Run Shaw Inst Clin Med, Key Lab Biotherapy Zhejiang Prov, Hangzhou 310016, Peoples R China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2009年第3期282-287,共6页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(30572155);Zhejiang Provincial Natural Science Foundation of China(R206060).

摘　　要：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. (Hepatobiliary Pancreat Dis Int 2009; 8: 282-287)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. (Hepatobiliary Pancreat Dis Int 2009; 8: 282-287)

关 键 词：hepatocellular carcinoma drug resistance oncolytic adenovirus CHEMOTHERAPY 

分 类 号：R735.7[医药卫生—肿瘤]