1. A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model.
- Author
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Guo K, Huang P, Xu N, Xu P, Kaku H, Zheng S, Xu A, Matsuura E, Liu C, and Kumon H
- Subjects
- Animals, Antineoplastic Agents administration & dosage, CD4-Positive T-Lymphocytes cytology, Cell Line, Tumor, Cell Proliferation, Cell Separation, Disease Models, Animal, Female, Flow Cytometry, Gene Expression Regulation, Neoplastic, Humans, Mice, Mice, Inbred BALB C, Neoplasm Metastasis, Neoplasm Transplantation, Survivin, T-Lymphocytes, Regulatory cytology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Renal Cell drug therapy, Imidazoles administration & dosage, Inhibitor of Apoptosis Proteins antagonists & inhibitors, Interleukin-2 administration & dosage, Kidney Neoplasms drug therapy, Naphthoquinones administration & dosage
- 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.
- Published
- 2015
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