Department of Urology, Seoul National University, Bundang Hospital, Seongnam‑si, Gyeonggi‑do 13620, Republic of Korea.
Department of Mechanical Engineering, KAIST, Daejeon 34141, Republic of Korea.
Oncol Rep. 2023 Jun;49(6). doi: 10.3892/or.2023.8567. Epub 2023 May 11.
CUDC‑907 is a novel inhibitor of phosphoinositide 3‑kinase and histone deacetylase. It exerts anticancer activities by inducing apoptosis and inhibiting the growth and metastases of various tumors. However, the anticancer effects of CUDC‑907 on bladder cancer have not been previously reported. Thus, the present study aimed to examine the anticancer effects of CUDC‑907 on 2D monolayer and 3D spheroid models of T24 cells established from highly malignant human grade III urinary bladder carcinoma and cisplatin‑resistant T24R2 cells generated by 17 months of exposure to cisplatin, starting at 0.01 µg/ml and increasing stepwise to 2 µg/ml. CUDC‑907 treatment significantly reduced the cell viabilities of the monolayer and spheroid cultures in a concentration‑dependent manner. The IC value of CUDC‑907 was higher in the bladder cancer spheroids than in the monolayers. Treatment with CUDC‑907 suppressed epithelial‑mesenchymal transition via decreasing vimentin and E‑cadherin and consequently inhibited the migration and invasion of the bladder cancer spheroids. In addition, it promoted apoptosis and increased the expression of apoptosis‑related genes, such as Bax and caspases. In conclusion, CUDC‑907 exerted anticancer effects by reducing the viability, migration and invasion, and inducing apoptosis of bladder cancer spheroids. These results suggest that CUDC‑907 is a potent agent for the treatment of bladder cancer.
CUDC-907 是一种新型的磷酸肌醇 3-激酶和组蛋白去乙酰化酶抑制剂。它通过诱导细胞凋亡和抑制各种肿瘤的生长和转移来发挥抗癌作用。然而,CUDC-907 对膀胱癌的抗癌作用尚未见报道。因此,本研究旨在研究 CUDC-907 对来源于高度恶性人 III 级膀胱癌的 T24 细胞的 2D 单层和 3D 球体模型以及通过在 0.01μg/ml 时开始并逐步增加至 2μg/ml 的顺铂暴露 17 个月而产生的顺铂耐药 T24R2 细胞的 2D 单层和 3D 球体模型的抗癌作用。CUDC-907 治疗以浓度依赖性方式显著降低了单层和球体培养物中的细胞活力。膀胱癌球体中的 CUDC-907 的 IC 值高于单层。CUDC-907 处理通过降低波形蛋白和 E-钙粘蛋白来抑制上皮-间充质转化,从而抑制膀胱癌球体的迁移和侵袭。此外,它促进了细胞凋亡并增加了凋亡相关基因,如 Bax 和半胱天冬酶的表达。总之,CUDC-907 通过降低膀胱癌球体的活力、迁移和侵袭以及诱导细胞凋亡来发挥抗癌作用。这些结果表明 CUDC-907 是治疗膀胱癌的有效药物。