Effects of Cabazitaxel in Renal Cell Carcinoma Cell Lines

Kosuke Mizutani, Masashi Tomoda, Yuta Ohno, Hideki Hayashi, Yasunori Fujita, Kyojiro Kawakami, Koji Kameyama, Taku Kato, Tadashi Sugiyama, Yoshinori Itoh, Masafumi Ito, Takashi Deguchi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6671-6677
Number of pages7
JournalAnticancer research
Volume35
Issue number12
Publication statusPublished - 01-12-2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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