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

  • Oncotarget. 2015 Aug 28;6(25):21137-47. doi: 10.18632/oncotarget.4121.
Kai Guo  1  2  3 ,  Peng Huang  1  2  3  4 ,  Naijin Xu  2  3 ,  Peng Xu  1  2  3 ,  Haruki Kaku  5 ,  Shaobo Zheng  1 ,  Abai Xu  1 ,  Eiji Matsuura  4 ,  Chunxiao Liu  1 ,  Hiromi Kumon  2  3  4
Affiliations
  • 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.
PMID: 26023798 DOI: 10.18632/oncotarget.4121
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.

Keywords
IVIS; MDSCs; Treg; YM155; interleukin-2; renal cell carcinoma.
Products