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

Research output: Contribution to journalArticle

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

Fingerprint

Renal Cell Carcinoma
Interleukin-2
Lung
Kidney
Neoplasms
Regulatory T-Lymphocytes
Cell Cycle Checkpoints
Tumor Burden
Luciferases
Therapeutics
interleukin 2 inhibitor
YM 155
Apoptosis
Neoplasm Metastasis
Pharmaceutical Preparations
Proteins

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model. / Guo, Kai; Huang, Peng; Xu, Naijin; Xu, Peng; Kaku, Haruki; Zheng, Shaobo; Xu, Abai; Matsuura, Eiji; Liu, Chunxiao; Kumon, Hiromi.

In: Oncotarget, Vol. 6, No. 25, 2015, p. 21136-21147.

Research output: Contribution to journalArticle

Guo, K, Huang, P, Xu, N, Xu, P, Kaku, H, Zheng, S, Xu, A, Matsuura, E, Liu, C & Kumon, H 2015, 'A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model', Oncotarget, vol. 6, no. 25, pp. 21136-21147.
Guo, Kai ; Huang, Peng ; Xu, Naijin ; Xu, Peng ; Kaku, Haruki ; Zheng, Shaobo ; Xu, Abai ; Matsuura, Eiji ; Liu, Chunxiao ; Kumon, Hiromi. / A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model. In: Oncotarget. 2015 ; Vol. 6, No. 25. pp. 21136-21147.
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AU - Kaku, Haruki

AU - Zheng, Shaobo

AU - Xu, Abai

AU - Matsuura, Eiji

AU - Liu, Chunxiao

AU - Kumon, Hiromi

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