Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan.
Environ Toxicol. 2021 Nov;36(11):2138-2145. doi: 10.1002/tox.23328. Epub 2021 Jul 19.
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.
膀胱癌（BC）是男性最常见的泌尿生殖系统肿瘤疾病之一，由于其易于转移的倾向，其生存率极低。抗癌药物氯喹（CQ）和羟基氯喹（HCQ）可能抑制肿瘤的进展和侵袭。然而，CQ 和 HCQ 影响 BC 的机制尚不确定。在这项研究中，CQ 和 HCQ 治疗通过调节基质金属蛋白酶-2（MMP-2）的表达抑制了两种 BC 细胞类型（5637 和 T24）的迁移和侵袭，MMP-2 属于基质 MMP 家族，是癌症进展的关键介质。此外，其他数据表明，用雷帕霉素处理用 CQ 或 HCQ 处理的 BC 细胞后，其迁移和侵袭作用被消除，雷帕霉素诱导自噬，表明 CQ 和 HCQ 在 BC 中的作用基于自噬抑制。总之，我们的研究表明，CQ 和 HCQ 通过靶向自噬功能下调 MMP-2 来调节 BC 中的细胞迁移，为 BC 的治疗提供了一种新的治疗策略。
