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

doi:10.18632/oncotarget.4121

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 journal › Article › peer-review

16 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 language	English
Pages (from-to)	21136-21147
Number of pages	12
Journal	Oncotarget
Volume	6
Issue number	25
DOIs	https://doi.org/10.18632/oncotarget.4121
Publication status	Published - 2015

Keywords

IVIS
Interleukin-2
MDSCs
Renal cell carcinoma
Treg
YM155

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.4121

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

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.",

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

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T1 - A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model

AU - Guo, Kai

AU - Huang, Peng

AU - Xu, Naijin

AU - Xu, Peng

AU - Kaku, Haruki

AU - Zheng, Shaobo

AU - Xu, Abai

AU - Matsuura, Eiji

AU - Liu, Chunxiao

AU - Kumon, Hiromi

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - IVIS

KW - Interleukin-2

KW - MDSCs

KW - Renal cell carcinoma

KW - Treg

KW - YM155

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SN - 1949-2553

VL - 6

SP - 21136

EP - 21147

JO - Oncotarget

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IS - 25

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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