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Inhibition of HeLa Cells by the Combination of Thioridazine and Oncolytic Adenovirus ZD55-TRAIL and the Exploration of Its Mechanism
Yang Dongmei1, Fang Xianlong2, Yang Yu2, Li Hongyan1, Pan Qiang1, Xu Haineng2*
1Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University,Hangzhou 310018, China; 2Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences,Chinese Academy
Abstract: Targeting Cancer Gene-Virotherapy is a newly developed method for cancer therapy. However， its efficiency still needs to be improved. In this study， we enhanced the cytotoxicity on HeLa cells with the combined use of clinical antipsychotic drug thioridazine and ZD55-TRAIL. Cytotoxicity of the combination of thioridazine and ZD55-TRAIL on HeLa cells was examined by MTT assay， direct observation and crystal violet staining. Hoechst33342 staining assay， flow cytometry experiments and Western blot assay were used to detect the occurrence of apoptosis in HeLa cells with the treatment of thioridazine and ZD55-TRAIL. We found that small molecule drug thioridazine combing with the virus ZD55-TRAIL could enhance the killing effect on HeLa cells. In addition， the results showed that the combined treatment led to lower level of anti-apoptotic XIAP protein and apoptosis was more obvious. This work firstly reported the inhibition effect of the combination of the antipsychotic drug thioridazine and ZD55-TRAIL on HeLa cells， and it could be a potential therapeutic approach for cervical cancer therapy in the future.
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