CUDC‑907 suppresses epithelial‑mesenchymal transition, migration and invasion in a 3D spheroid model of bladder cancer.

Oncology reports(2023)

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摘要
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.
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关键词
bladder cancer spheroid, CUDC-907, epithelial-mesenchymal transition, migration, invasion
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