Department of Urology, The Fifth Affiliated Hospital Sun Yat-sen University, Zhuhai, 519000 Guangdong, P.R. China.
Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001 Anhui, China.
Biochem Cell Biol. 2022 Apr;100(2):179-187. doi: 10.1139/bcb-2021-0552. Epub 2022 Feb 15.
Platinum-based chemotherapy is a widely used strategy for bladder cancer (BCa) treatment. However, its clinical efficacy is affected by chemotherapy resistance via complex molecular mechanisms. Therefore, there is an urgent need to explore new targets for BCa therapy. Here, we showed that bromodomain-4 protein (BRD4) expression is upregulated in BCa tissues and cells. Inhibition of BRD4 attenuated the migration and invasion of BCa cells, which was rescued by the Sonic hedgehog (SHH) pathway activator recombinant human Sonic hedgehog peptide (rhSHH). We further found that cisplatin (DDP) suppressed the migration and invasion of BCa cells in vitro and inhibited tumor growth in vivo. However, overexpression of BRD4 weakened the pharmacological effects of DDP. In brief, our research revealed that BRD4 promotes migration and invasion by positively regulating the SHH pathway, drives DDP resistance in BCa, and is a novel therapeutic target for the treatment of BCa.
铂类化疗是膀胱癌 (BCa) 治疗的常用策略。然而，其临床疗效受到通过复杂分子机制产生的化疗耐药性的影响。因此，迫切需要探索 BCa 治疗的新靶点。在这里，我们表明 BRD4 蛋白 (BRD4) 在 BCa 组织和细胞中表达上调。抑制 BRD4 减弱了 BCa 细胞的迁移和侵袭，而 Sonic hedgehog (SHH) 通路激活剂重组人 Sonic hedgehog 肽 (rhSHH) 可挽救这种作用。我们进一步发现顺铂 (DDP) 抑制了体外 BCa 细胞的迁移和侵袭，并抑制了体内肿瘤生长。然而，BRD4 的过表达削弱了 DDP 的药理作用。总之，我们的研究表明 BRD4 通过正向调控 SHH 通路促进迁移和侵袭，导致 BCa 对 DDP 的耐药性，并为 BCa 的治疗提供了一个新的治疗靶点。
