title: Effects of Cabazitaxel in Renal Cell Carcinoma Cell Lines.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan mizutech@gifu-u.ac.jp.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mizutani
authors.affiliation: Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tomoda
authors.affiliation: Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Department of Pharmacy, Gifu University Hospital, Gifu, Japan Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology Itabashi-ku, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology Itabashi-ku, Tokyo, Japan.
authors.forename: Kyojiro
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kameyama
authors.affiliation: Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kato
authors.affiliation: Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Pharmacy, Gifu University Hospital, Gifu, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology Itabashi-ku, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Deguchi
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D043823:Taxoids; C552428:cabazitaxel
keywords: AKT; Caki-1; KMRC-1; OS-RC-2; Renal cell carcinoma; cabazitaxel; docetaxel; p-glycoprotein