Bladder cancer (BC), one of the most common urological neoplastic disorders in men, has an extremely low survival rate because of its tendency to metastasize. The anticancer drugs chloroquine (CQ) and hydroxy CQ (HCQ) might inhibit tumor progression and invasiveness. However, the mechanism by which CQ and HCQ influence BC is undetermined. In this study, CQ and HCQ treatments inhibited the migration and invasion of two BC cell types (5637 and T24) through expression modulation of matrix metalloproteinase-2 (MMP-2), which belongs to the matrix MMP family and is a key mediator of cancer progression. Moreover, additional data revealed that the migrative and invasive effects of BC cells treated with CQ or HCQ were abolished after treatment with rapamycin, which induces autophagy, demonstrating that CQ and HCQ functions in BC are based on autophagy inhibition. In conclusion, our research demonstrated that CQ and HCQ regulated cell motility in BC through MMP-2 downregulation by targeting autophagy functions, providing a novel therapeutic strategy for BC treatment.

中文翻译：

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氯喹和羟氯喹通过靶向基质金属蛋白酶 2 表达减弱对膀胱癌侵袭潜力的影响

膀胱癌 (BC) 是男性最常见的泌尿系统肿瘤疾病之一，由于容易转移，因此存活率极低。抗癌药物氯喹 (CQ) 和羟基 CQ (HCQ) 可能会抑制肿瘤进展和侵袭。然而，CQ 和 HCQ 影响 BC 的机制尚未确定。在本研究中，CQ 和 HCQ 处理通过基质金属蛋白酶-2 (MMP-2) 的表达调节抑制两种 BC 细胞类型（5637 和 T24）的迁移和侵袭，基质金属蛋白酶 2 属于基质 MMP 家族，是癌症进展。此外，额外的数据显示，用诱导自噬的雷帕霉素处理后，用 CQ 或 HCQ 处理的 BC 细胞的迁移和侵袭作用被消除，证明 BC 中的 CQ 和 HCQ 功能基于自噬抑制。总之，我们的研究表明，CQ 和 HCQ 通过靶向自噬功能通过 MMP-2 下调来调节 BC 中的细胞运动，为 BC 治疗提供了一种新的治疗策略。