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

作者：Guo, Kai; Huang, Peng^*; Xu, Naijin; Xu, Peng; Kaku, Haruki; Zheng, Shaobo; Xu, Abai; Matsuura, Eiji; Liu, Chunxiao; Kumon, Hiromi

来源：Oncotarget, 2015, 6(25): 21137-21147.

DOI：10.18632/oncotarget.4121

• renal cell carcinoma
• YM155
• interleukin-2
• IVIS
• Treg
• MDSCs

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.

• 出版日期2015-8-28
• 单位南方医科大学