A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma

Hiroki Iwata, Hiromi Sato, Rina Suzuki, Ryota Yamada, Saki Ichinomiya, Midori Yanagihara, Hiroyuki Okabe, Yuko Sekine, Tomohiro Yano, Koichi Ueno

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Renal cell carcinoma (RCC) is resistant to chemotherapy partly due to the overexpression of the P-glycoprotein. Several tumor suppressor genes have been reported to be silenced by hypermethylation of the promoter region in RCC. We recently reported that the in vitro cytotoxicity of vinblastine (VBL) was enhanced by pre-treatment with the demethylating agent, 5-aza-2′- deoxycytidine (Aza), in the RCC cell line, Caki-1. In this study, we investigated the combined effect of Aza and VBL in a Caki-1 xenograft model and in other RCC cell lines in vitro. In the xenograft model, tumor volume and weight were significantly suppressed in the co-treatment group, compared to the control, and the expressions of P-glycoprotein, Bcl-2 and cyclin B1 were reduced. Thus, this combined effect could be mediated by the accumulation of intracellular VBL and the enhancement of apoptosis and cell cycle arrest. Moreover, the cytotoxicity of VBL was enhanced in vitro in three RCC cell lines by Aza treatment. These findings suggest that the combination treatment with Aza and VBL is effective against RCC.

Original languageEnglish
Pages (from-to)1653-1661
Number of pages9
JournalInternational journal of oncology
Volume38
Issue number6
DOIs
Publication statusPublished - 2011 Jun
Externally publishedYes

Keywords

  • 5-Aza-2′-deoxycytidine
  • Combined effect
  • Renal cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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