Effects Of Adenosine On Apoptosis Of Ovarian Cancer A2780 Cells Via ROS And Caspase Pathways

OncoTargets and Therapy

卷:Volume 12

关键词: adenosine;    apoptosis;    ros;    caspase pathway;    ovarian cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Bing Xia, Jing Wang Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Central South University, Changsha 410078, People’s Republic of ChinaCorrespondence: Jing WangHunan Cancer Hospital, the Affiliated Tumor Hospital of Xiang-Ya School of Medicine, Central South University, Changsha 410078, People’s Republic of ChinaTel [phone]Email [e-mail]: Ovarian cancer is the second most common malignant tumor of the female genital tract and the main cause of death of gynecological malignant tumors. Exogenous adenosine has been shown to induce apoptosis in tumor cells.Materials and methods: The current study aimed to investigate the inhibitory effect and underlying mechanism of adenosine on the proliferation of ovarian cancer cells. The inhibitory effects of adenosine on ovarian cancer cells were assessed through MTT assay. The adenosine-induced apoptosis was determined by Hoechst 33342 staining and flow cytometry. The effect of adenosine on the intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) was assessed according to the DCFH-DA and JC-1 methods, respectively. Expression of apoptosis-related proteins and mitochondrial proteins was measured using Western blotting.Results: MTT suggested that adenosine inhibited A2780 and SKOV3 cells viability in a dose- and time-dependent manner (P<0.05). Hoechst 33342 staining had demonstrated pronounced changes in cell morphology; to be specific, cells treated with 0 mmol/L adenosine showed a light blue color, while those in treatment groups had nuclear pyknosis and apoptotic body formation. Besides, the apoptosis rate was positively correlated with adenosine concentration (P<0.05). Flow cytometry results revealed that adenosine increased the intracellular ROS level and decreased MMP. Western blotting indicated that, the expression of Bax, cleaved-caspase-3 and cleaved-poly (ADP-ribose) polymerase was up-regulated with the increase in adenosine concentration, while that of Bcl-2 protein and apoptosis-related protein caspase-3 was down-regulated.Conclusion: With the increase in drug concentration, the CytoC expression in mitochondria was gradually reduced, while that in the cytoplasm was gradually increased. In conclusion, Ado may inhibit the proliferation and induce the apoptosis of ovarian cancer cells by increasing ROS, up-regulating the pro-apoptotic protein Bax and activating the caspase-3 expression in vitro.Keywords: adenosine, apoptosis, ROS, caspase pathway, ovarian cancer

【 授权许可】

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