RRC ID 39061
著者 Mizutani K, Tomoda M, Ohno Y, Hayashi H, Fujita Y, Kawakami K, Kameyama K, Kato T, Sugiyama T, Itoh Y, Ito M, Deguchi T.
タイトル Effects of Cabazitaxel in Renal Cell Carcinoma Cell Lines.
ジャーナル Anticancer Res
Abstract 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.
巻・号 35(12)
ページ 6671-7
公開日 2015-12-1
PII 35/12/6671
PMID 26637883
MeSH Carcinoma, Renal Cell / drug therapy* Cell Line, Tumor Cell Proliferation Humans Taxoids / administration & dosage Taxoids / therapeutic use*
IF 1.994
引用数 4
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 OS-RC-2(RCB0735)