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

  • Authors:
    • Hiroki Iwata
    • Hiromi Sato
    • Rina Suzuki
    • Ryota Yamada
    • Saki Ichinomiya
    • Midori  Yanagihara
    • Hiroyuki Okabe
    • Yuko Sekine
    • Tomohiro Yano
    • Koichi Ueno
  • View Affiliations

  • Published online on: April 6, 2011     https://doi.org/10.3892/ijo.2011.999
  • Pages: 1653-1661
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

Related Articles

Journal Cover

June 2011
Volume 38 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Iwata H, Sato H, Suzuki R, Yamada R, Ichinomiya S, Yanagihara M, Okabe H, Sekine Y, Yano T, Ueno K, Ueno K, et al: A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma. Int J Oncol 38: 1653-1661, 2011
APA
Iwata, H., Sato, H., Suzuki, R., Yamada, R., Ichinomiya, S., Yanagihara, M. ... Ueno, K. (2011). A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma. International Journal of Oncology, 38, 1653-1661. https://doi.org/10.3892/ijo.2011.999
MLA
Iwata, H., Sato, H., Suzuki, R., Yamada, R., Ichinomiya, S., Yanagihara, M., Okabe, H., Sekine, Y., Yano, T., Ueno, K."A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma". International Journal of Oncology 38.6 (2011): 1653-1661.
Chicago
Iwata, H., Sato, H., Suzuki, R., Yamada, R., Ichinomiya, S., Yanagihara, M., Okabe, H., Sekine, Y., Yano, T., Ueno, K."A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma". International Journal of Oncology 38, no. 6 (2011): 1653-1661. https://doi.org/10.3892/ijo.2011.999