PKCα and Netrin-1/UNC5B positive feedback control in relation with chemical therapy in bladder cancer

J. Liu, J. Li

Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, China. mskongchuize@sina.com

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• Oncology

OBJECTIVE: To explore the cisplatin medical tolerance mechanism affecting bladder cancer cells.

MATERIALS AND METHODS: Bladder cancer cells were treated with protein kinase C α (PKCα) stimulation and inhibition agents. The small-interfering RNA (siRNA) inhibitory technique was used to differentiate and remove Netrin-1 from UNC5B. Cells treated by cisplatin were processed by the MIT method to estimate cell death and growth rate. The Western blot method was utilized to analyze PKCα, netrin-1, and UNC5B in bladder cancer cells, used in the relative control sample. Co-immunoprecipitation was employed to analyze PKCα, netrin-1, and UNC5B combination effects.

RESULTS: PKCα high activity, netrin-1 high expression, and UNC5B with low expression can enhance bladder cancer cells cisplatin medical tolerance. PKCα low activity, netrin-1 low expression, and UNC5B with high expression can also enhance bladder cancer cells sensitivity to chemical therapeutic treatments. PKCα high activity with enhanced netrin-1 reduced UNC5B expression, and also enhanced netrin-1/UNC5B combination. It inhibits and/or deletes PKCα, Netrin-1 lower stream extracellular regulated protein kinases (ERK) signal, deletes UNC5B, PKCα, and lowers stream (ERK) signaling from activity.

CONCLUSIONS: PKCα and netrin-1/UNC5B form a positive feedback control loop in relation to the regulation of cisplatin in bladder cancer cells.

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