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<p>Epigenetic alterations are emerging as a major driver of acquired cisplatin (CDDP) resistance in bladder cancer (BCa). The study investigated whether GSK343, an inhibitor of Enhancer of Zeste Homolog 2 (EZH2), can overcome CDDP resistance in BCa. CDDP-resistant T24 and 5637 cells were treated GSK343 (5, 10, or 20µM) for 48&#xa0;h. Cell viability was assessed using CCK-8 assays, clonogenic survival using colony formation assays, migration capacity using wound healing (scratch) assays, invasion using Transwell assays, and apoptosis using flow cytometry. CDDP-resistant cells exhibited significantly higher EZH2 and H3K27me3 expression levels than parental T24 and 5637 cells. Treatment with 20 µM GSK343 markedly reduced EZH2 and H3K27me3 expression in resistant cells compared to vehicle control, with greater efficacy than lower concentrations (5 or 10 µM). Following 20 µM GSK343 treatment, resistant cells showed significantly reduced viability, fewer colonies, impaired migration, and decreased invasion compared to vehicle control. Furthermore, the apoptosis rate was significantly increased in resistant cells treated with 20 µM GSK343. The study demonstrates that GSK343 inhibits EZH2-mediated H3K27me3 and overcomes acquired CDDP resistance in BCa cells, suggesting its therapeutic potential for BCa patients with limited benefit from chemotherapy.</p>

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GSK343, an inhibitor of EZH2, prevents acquired cisplatin resistance in bladder cancer

  • 期刊论文

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  • 发表日期：

    2025年6月23日

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  • Liang He,
  • Peng Liu

摘要

Epigenetic alterations are emerging as a major driver of acquired cisplatin (CDDP) resistance in bladder cancer (BCa). The study investigated whether GSK343, an inhibitor of Enhancer of Zeste Homolog 2 (EZH2), can overcome CDDP resistance in BCa. CDDP-resistant T24 and 5637 cells were treated GSK343 (5, 10, or 20µM) for 48 h. Cell viability was assessed using CCK-8 assays, clonogenic survival using colony formation assays, migration capacity using wound healing (scratch) assays, invasion using Transwell assays, and apoptosis using flow cytometry. CDDP-resistant cells exhibited significantly higher EZH2 and H3K27me3 expression levels than parental T24 and 5637 cells. Treatment with 20 µM GSK343 markedly reduced EZH2 and H3K27me3 expression in resistant cells compared to vehicle control, with greater efficacy than lower concentrations (5 or 10 µM). Following 20 µM GSK343 treatment, resistant cells showed significantly reduced viability, fewer colonies, impaired migration, and decreased invasion compared to vehicle control. Furthermore, the apoptosis rate was significantly increased in resistant cells treated with 20 µM GSK343. The study demonstrates that GSK343 inhibits EZH2-mediated H3K27me3 and overcomes acquired CDDP resistance in BCa cells, suggesting its therapeutic potential for BCa patients with limited benefit from chemotherapy.