Sunitinib enhances antitumor effects against chemotherapy-resistant bladder cancer through suppression of ERK1/2 phosphorylation

  • Authors:
    • Ario Takeuchi
    • Masatoshi Eto
    • Masaki Shiota
    • Katsunori Tatsugami
    • Akira Yokomizo
    • Kentaro Kuroiwa
    • Momoe Itsumi
    • Seiji Naito
  • View Affiliations

  • Published online on: February 13, 2012     https://doi.org/10.3892/ijo.2012.1368
  • Pages: 1691-1696
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Bladder cancer patients who are refractory to chemotherapy have a poor prognosis. Furthermore, additional chemotherapies provide little benefit to patients who have relapsed after an initial response. Recently, it was reported that several molecular pathways are implicated in bladder carcinogenesis, including the epidermal growth factor receptor (EGFR) pathway, the vascular endothelial growth factor (VEGF) pathway and the Ras-MAPK pathway. We hypothesized that sunitinib would be effective in bladder cancer as it is an oral inhibitor of multiple receptor tyrosine kinases, including VEGF receptors, platelet derived growth factor (PDGF) receptors and stem cell factor receptor (c-KIT), and is a standard first-line treatment of advanced clear cell renal carcinoma. In the present study, the antiproliferative effects of sunitinib were clearly demonstrated in KK47, KK47/DDP20 and KK47/ADR cell lines in vitro due to the suppression of ERK1/2 phosphorylation. In a mouse model, the antitumor effects of sunitinib were again clearly seen. Also, treatment with sunitinib decreased the abundance of regulatory T cells (Tregs). However, cytotoxic T lymphocyte (CTL) activity was not induced sufficiently as compared with an IFN-α-treated group. Our results suggested that sunitinib was effective in chemotherapy-resistant bladder cancer patients. On the other hand, these findings provided the rationale for combination therapy with sunitinib and immune-based cancer therapy for advanced malignancies to prevent the occurrence of rebound phenomena.

Related Articles

Journal Cover

May 2012
Volume 40 Issue 5

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
Takeuchi A, Eto M, Shiota M, Tatsugami K, Yokomizo A, Kuroiwa K, Itsumi M and Naito S: Sunitinib enhances antitumor effects against chemotherapy-resistant bladder cancer through suppression of ERK1/2 phosphorylation. Int J Oncol 40: 1691-1696, 2012
APA
Takeuchi, A., Eto, M., Shiota, M., Tatsugami, K., Yokomizo, A., Kuroiwa, K. ... Naito, S. (2012). Sunitinib enhances antitumor effects against chemotherapy-resistant bladder cancer through suppression of ERK1/2 phosphorylation. International Journal of Oncology, 40, 1691-1696. https://doi.org/10.3892/ijo.2012.1368
MLA
Takeuchi, A., Eto, M., Shiota, M., Tatsugami, K., Yokomizo, A., Kuroiwa, K., Itsumi, M., Naito, S."Sunitinib enhances antitumor effects against chemotherapy-resistant bladder cancer through suppression of ERK1/2 phosphorylation". International Journal of Oncology 40.5 (2012): 1691-1696.
Chicago
Takeuchi, A., Eto, M., Shiota, M., Tatsugami, K., Yokomizo, A., Kuroiwa, K., Itsumi, M., Naito, S."Sunitinib enhances antitumor effects against chemotherapy-resistant bladder cancer through suppression of ERK1/2 phosphorylation". International Journal of Oncology 40, no. 5 (2012): 1691-1696. https://doi.org/10.3892/ijo.2012.1368