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

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Research Papers:

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 and Hiromi Kumon

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Oncotarget. 2015; 6:21137-21147. https://doi.org/10.18632/oncotarget.4121

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Abstract

Kai Guo1,2,3,*, Peng Huang1,2,3,4, Naijin Xu2,3,*, Peng Xu1,2,3, Haruki Kaku5, Shaobo Zheng1, Abai Xu1, Eiji Matsuura4, Chunxiao Liu1 and Hiromi Kumon2,3,4

1 Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China

2 Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

3 Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan

4 Okayama Medical Innovation Center, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

5 Department of Urology, Okamura Isshindow Hospital, Okayama, Japan

* These authors contributed to the work equally and should be regarded as co-first authors

Correspondence to:

Peng Huang, email:

Keywords: renal cell carcinoma, YM155, interleukin-2, IVIS, Treg, MDSCs

Received: November 30, 2014 Accepted: May 02, 2015 Published: May 12, 2015

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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Research Papers:

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

Abstract