PMID- 26637883 OWN - NLM STAT- MEDLINE DCOM- 20160428 LR - 20151206 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 35 IP - 12 DP - 2015 Dec TI - Effects of Cabazitaxel in Renal Cell Carcinoma Cell Lines. PG - 6671-7 AB - BACKGROUND/AIM: Advanced renal cell carcinoma is treated with mammalian target of rapamycin (mTOR) inhibitors or tyrosine kinase inhibitors (TKIs). The effects of these drugs are, however, limited and novel treatment strategies are required. Clear-cell type renal cell carcinoma (ccRCC) is chemo-resistant, in part, due to expression of multidrug resistance proteins such as p-glycoprotein. Cabazitaxel, a tubulin-binding taxane drug used for castration-resistant prostate cancer, has less affinity for p-glycoprotein compared to docetaxel. In the current study, the effects of docetaxel and cabazitaxel on ccRCC cells were investigated. MATERIALS AND METHODS: The expression of p-glycoprotein was evaluated in the ccRCC cell lines, Caki-1, KMRC-1 and OS-RC-2 by western blotting. Cells were treated with cabazitaxel or docetaxel, and growth kinetics and tubulin polymerization were determined by the WST-1 assay and cell-based tubulin polymerization assay, respectively. Intracellular drug concentrations were measured by chromatography. AKT activation after treatment was examined by western blotting. RESULTS: All ccRCC cell lines expressed p-glycoprotein. Cabazitaxel inhibited cell growth and induced tubulin polymerization more potently than docetaxel. The intracellular concentration of cabazitaxel was much higher than docetaxel in all cell lines. Both docetaxel and cabazitaxel inhibit AKT phosphorylation at 5 min among three cells. CONCLUSION: Cabazitaxel inhibits growth of ccRCC cells expressing p-glycoprotein and could thus be possibly used for advanced ccRCC patients in combination with targeted-therapy enhancing their effects. CI - Copyright(c) 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. FAU - Mizutani, Kosuke AU - Mizutani K AD - Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan mizutech@gifu-u.ac.jp. FAU - Tomoda, Masashi AU - Tomoda M AD - Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Ohno, Yuta AU - Ohno Y AD - Department of Pharmacy, Gifu University Hospital, Gifu, Japan. FAU - Hayashi, Hideki AU - Hayashi H AD - Department of Pharmacy, Gifu University Hospital, Gifu, Japan Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan. FAU - Fujita, Yasunori AU - Fujita Y AD - Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology Itabashi-ku, Tokyo, Japan. FAU - Kawakami, Kyojiro AU - Kawakami K AD - Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology Itabashi-ku, Tokyo, Japan. FAU - Kameyama, Koji AU - Kameyama K AD - Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Kato, Taku AU - Kato T AD - Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Sugiyama, Tadashi AU - Sugiyama T AD - Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan. FAU - Itoh, Yoshinori AU - Itoh Y AD - Department of Pharmacy, Gifu University Hospital, Gifu, Japan. FAU - Ito, Masafumi AU - Ito M AD - Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology Itabashi-ku, Tokyo, Japan. FAU - Deguchi, Takashi AU - Deguchi T AD - Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Taxoids) RN - 51F690397J (cabazitaxel) SB - IM MH - Carcinoma, Renal Cell/*drug therapy MH - Cell Line, Tumor MH - Cell Proliferation MH - Humans MH - Taxoids/administration & dosage/*therapeutic use OTO - NOTNLM OT - AKT OT - Caki-1 OT - KMRC-1 OT - OS-RC-2 OT - Renal cell carcinoma OT - cabazitaxel OT - docetaxel OT - p-glycoprotein EDAT- 2015/12/08 06:00 MHDA- 2016/04/29 06:00 CRDT- 2015/12/06 06:00 PHST- 2015/12/06 06:00 [entrez] PHST- 2015/12/08 06:00 [pubmed] PHST- 2016/04/29 06:00 [medline] AID - 35/12/6671 [pii] PST - ppublish SO - Anticancer Res. 2015 Dec;35(12):6671-7.