Combination treatment with cyclosporin A and arsenic trioxide induce synergistic cell death via non-apoptotic pathway in uterine cervical cancer cells

环孢素A与三氧化二砷联合治疗通过非凋亡途径诱导宫颈癌细胞协同细胞死亡

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作者:Pei-Ju Wu, I-Lun Hsin, Wei-Li Hung, Maw-Sheng Lee, Po-Hui Wang, Jiunn-Liang Ko

Abstract

Cyclosporin A is an immunosuppressive drug with anti-cancer effect. Arsenic trioxide (As2O3), a well-known cancer-inhibiting drug, induced cytotoxicity via apoptosis and autophagy. The aim of this study is to evaluate the effect of combinational treatment with cyclosporin A and arsenic trioxide on cell viability inhibition in cervical cancer cells. Using MTT assay and combination index, combinational treatment with cyclosporin A and arsenic trioxide induced a synergistic cytotoxic effect in Caski and SiHa cells. Cyclosporin A and arsenic trioxide triggered cell death via non-apoptotic pathway by using annexin V/propidium iodide (PI) assay. Cyclosporin A and arsenic trioxide combined treatment decreased mitochondrial membrane potential and increase reactive oxygen species (ROS) generation. This co-treatment increased LC3B-II expression and autophagosome formation in cervical cancer cells. This study first demonstrated that combinational treatment with cyclosporin A and As2O3 trigger synergistic cytotoxic effect via autophagy in cervical cancer cells.

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