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首页> 外文期刊>Cellular Physiology and Biochemistry >Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis
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Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis

机译：氯喹通过抑制自噬和激活细胞凋亡来增强膀胱癌细胞的放射敏感性

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Background/Aims Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. Methods Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors. Cell apoptosis was detected by flow cytometry and western blot. Radiation-induced DNA double strand break was measured by the staining of γ-H2AX. In addition, autophagy was detected by western blot, immunofluorescence staining, and electron microscopy. Results The treatment with chloroquine alone inhibited the proliferation of bladder cancer cells in a dose-dependent manner. Low cytotoxic concentrations of chloroquine enhanced the radiation sensitivity of bladder cancer cells with a sensitization enhancement ratio of 1.53 and 1.40. Chloroquine also obviously weakened the repair of radiation-induced DNA damage. A combination of radiation and chloroquine enhanced the apoptosis rate of EJ and T24 cells and down-regulated the expression of Bcl-2 while up-regulating the expression of caspase-3. Additionally, the relevant markers of autophagy were obviously increased in the combined group, meaning that chloroquine inhibited autophagy induced by irradiation. Furthermore, subcutaneous xenograft tumors displayed that the combination of radiation and chloroquine could impede tumorigenesis in vivo. Conclusion In summary, these results provided support that by inhibiting autophagy and activating apoptosis, chloroquine might be a potentially promising radiosensitizer in the radiation therapy of bladder cancer.
机译：背景/目的氯喹以前用作抗疟疾药物，但现已证明可用于多种疾病。本研究旨在研究氯喹对膀胱癌的放射增敏作用，重点是自噬抑制和凋亡诱导。方法用或不用氯喹照射膀胱癌细胞系。通过细胞计数试剂盒8测定法测定细胞增殖。氯喹的放射增敏作用通过异种移植瘤的克隆形成存活和进展来评估。通过流式细胞术和蛋白质印迹检测细胞凋亡。通过γ-H2AX染色来测量辐射诱导的DNA双链断裂。另外，通过蛋白质印迹，免疫荧光染色和电子显微镜检测自噬。结果单独用氯喹治疗可以剂量依赖性地抑制膀胱癌细胞的增殖。低细胞毒性浓度的氯喹以1.53和1.40的敏化增强比增强了膀胱癌细胞的放射敏感性。氯喹还明显削弱了辐射诱导的DNA损伤的修复。放射线和氯喹的组合可提高EJ和T24细胞的凋亡率，并下调Bcl-2的表达，而上调caspase-3的表达。此外，联合组的自噬相关标志物明显增加，这意味着氯喹抑制了辐射诱导的自噬。此外，皮下异种移植肿瘤显示，放射线和氯喹的组合可在体内阻碍肿瘤发生。结论总而言之，这些结果提供了支持，即通过抑制自噬和激活细胞凋亡，氯喹可能成为膀胱癌放射治疗中潜在的有希望的放射增敏剂。

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