synergistic suppression effect on tumor growth of ovarian cancer by combining cisplatin with a manganese superoxide dismutase-armed oncolytic adenovirus

Shibing Wang,1,2,* Jing Shu,3,* Li Chen,4 Xiaopan Chen,3 Jianhong Zhao,4 Shuangshuang Li,1,2 Xiaozhou Mou,1,2 Xiangmin Tong1,2 1Clinical Research Institute, Zhejiang Provincial People’s Hospital, 2Key Laboratory of Cancer Molecular Diagnosis and Individualized Therapy of Zhejiang Province, 3Department of Reproductive Endocrinology, Zhejiang Provincial People’s Hospital, 4Department of Obstetrics and Gynecology, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Gene therapy on the basis of oncolytic adenovirus is a novel approach for human cancer therapeutics. We aim to investigate whether it will synergistically reinforce their antiovarian cancer activities when the combined use of ZD55-manganese superoxide dismutase (MnSOD) and cisplatin was performed. The experiments in vitro showed that ZD55-MnSOD enhances cisplatin-induced apoptosis and causes remarkable ovarian cancer cell death. Apoptosis induction by treatment with ZD55-MnSOD and/or cisplatin was detected in SKOV-3 by apoptotic cell staining, flow cytometry, and western blot analysis. In addition, the cytotoxicity caused by ZD55-MnSOD to normal cells was examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and western blot analysis. Animal experiment further confirmed that combination of ZD55-MnSOD and cisplatin achieved significant inhibition of SKOV-3 ovarian tumor xenografted growth. In summary, we have demonstrated that ZD55-MnSOD can sensitize human ovarian cancer cells to cisplatin-induced cell death and apoptosis in vitro and in vivo. These findings indicate that the combined treatment with ZD55-MnSOD and cisplatin could represent a rational approach for antiovarian cancer therapy. Keywords: oncolytic adenovirus, MnSOD, cisplatin, ovarian cancer