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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • CD4-Positive T-Lymphocytes / cytology
  • Carcinoma, Renal Cell / drug therapy*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Separation
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Imidazoles / administration & dosage*
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
  • Interleukin-2 / administration & dosage*
  • Kidney Neoplasms / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Naphthoquinones / administration & dosage*
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Survivin
  • T-Lymphocytes, Regulatory / cytology

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Imidazoles
  • Inhibitor of Apoptosis Proteins
  • Interleukin-2
  • Naphthoquinones
  • Survivin
  • sepantronium