Drug Design, Development and Therapy (Nov 2016)
Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma
Abstract
Chunhua Yang,1,2 Hang Cao,1 Ning Liu,1 Kai Xu,1 Meng Ding,1 Li-jun Mao1 1Department of Urinary Surgery, The Affiliated Hospital of Xuzhou Medical University, 2Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, People’s Republic of China Abstract: Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18, and these were not affected by DTIC. ZD55-IL-18 enhanced the cytotoxicity of DTIC accompanied by increased apoptosis. Moreover, ZD55-IL-18 and DTIC synergistically inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited vascular endothelial growth factor expression and lung metastasis in xenografts of nude mice. In conclusion, this is the first study to show synergistic anticancer activity of ZD55-IL-18 and DTIC for malignant melanoma. Our results provide evidence that chemo-gene-viro therapeutic approach has greater potential for malignant cancers than conventional chemotherapy or gene therapy. Keywords: melanoma, IL-18, dacarbazine, oncolytic adenovirus
