A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model

Kai Guo, Peng Huang, Naijin Xu, Peng Xu, Haruki Kaku, Shaobo Zheng, Abai Xu, Eiji Matsuura, Chunxiao Liu, Hiromi Kumon

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11 Citations (Scopus)

Abstract

YM155, a small molecule inhibitor of the antiapoptotic protein survivin, has been developed as a potential anti-cancer drug. We investigated a combination therapy of YM155 and interleukin-2 (IL-2) in a mouse model of renal cell carcinoma (RCC). YM155 caused cell cycle arrest and apoptosis in renal cancer (RENCA) cells. Next, luciferase-expressing RENCA cells were implanted in the left kidney and the lung of BALB/c mice to develop RCC metastatic model. In this orthotopic renal and metastatic lung tumors models, YM155 and IL-2 additively decreased tumor weight, lung metastasis, and luciferin-stained tumor images. Also, the combination significantly suppressed regulatory T cells and myeloid-derived suppressor cells compared with single agent treatment. We suggest that a combination of YM155 and IL-2 can be tested as a potential therapeutic modality in patients with RCC.

Original languageEnglish
Pages (from-to)21136-21147
Number of pages12
JournalOncotarget
Volume6
Issue number25
Publication statusPublished - 2015

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Keywords

  • Interleukin-2
  • IVIS
  • MDSCs
  • Renal cell carcinoma
  • Treg
  • YM155

ASJC Scopus subject areas

  • Oncology

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