PMID- 32141538 OWN - NLM STAT- MEDLINE DCOM- 20210301 LR - 20210301 IS - 2284-0729 (Electronic) IS - 1128-3602 (Linking) VI - 24 IP - 4 DP - 2020 Feb TI - PKCalpha and Netrin-1/UNC5B positive feedback control in relation with chemical therapy in bladder cancer. PG - 1712-1717 LID - 20346 [pii] LID - 10.26355/eurrev_202002_20346 [doi] AB - OBJECTIVE: To explore the cisplatin medical tolerance mechanism affecting bladder cancer cells. MATERIALS AND METHODS: Bladder cancer cells were treated with protein kinase C alpha (PKCalpha) 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 PKCalpha, netrin-1, and UNC5B in bladder cancer cells, used in the relative control sample. Co-immunoprecipitation was employed to analyze PKCalpha, netrin-1, and UNC5B combination effects. RESULTS: PKCalpha high activity, netrin-1 high expression, and UNC5B with low expression can enhance bladder cancer cells cisplatin medical tolerance. PKCalpha low activity, netrin-1 low expression, and UNC5B with high expression can also enhance bladder cancer cells sensitivity to chemical therapeutic treatments. PKCalpha high activity with enhanced netrin-1 reduced UNC5B expression, and also enhanced netrin-1/UNC5B combination. It inhibits and/or deletes PKCalpha, Netrin-1 lower stream extracellular regulated protein kinases (ERK) signal, deletes UNC5B, PKCalpha, and lowers stream (ERK) signaling from activity. CONCLUSIONS: PKCalpha and netrin-1/UNC5B form a positive feedback control loop in relation to the regulation of cisplatin in bladder cancer cells. FAU - Liu, J AU - Liu J AD - Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, China. mskongchuize@sina.com. FAU - Li, J AU - Li J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Italy TA - Eur Rev Med Pharmacol Sci JT - European review for medical and pharmacological sciences JID - 9717360 RN - 0 (Antineoplastic Agents) RN - 0 (NTN1 protein, human) RN - 0 (Naphthalenes) RN - 0 (Netrin Receptors) RN - 0 (UNC5B protein, human) RN - 158651-98-0 (Netrin-1) RN - EC 2.7.11.13 (PRKCA protein, human) RN - EC 2.7.11.13 (Protein Kinase C-alpha) RN - I271P23G24 (calphostin C) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Cell Line, Tumor MH - Cisplatin/*pharmacology MH - Feedback, Physiological MH - Humans MH - Naphthalenes/pharmacology MH - Netrin Receptors/*metabolism MH - Netrin-1/*metabolism MH - Protein Kinase C-alpha/*metabolism MH - Urinary Bladder Neoplasms/drug therapy/*metabolism EDAT- 2020/03/07 06:00 MHDA- 2021/03/02 06:00 CRDT- 2020/03/07 06:00 PHST- 2020/03/07 06:00 [entrez] PHST- 2020/03/07 06:00 [pubmed] PHST- 2021/03/02 06:00 [medline] AID - 20346 [pii] AID - 10.26355/eurrev_202002_20346 [doi] PST - ppublish SO - Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):1712-1717. doi: 10.26355/eurrev_202002_20346.