title: A combination of YM-155, a small molecule survivin inhibitor, and IL-2 potently suppresses renal cell carcinoma in murine model.
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.
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.|Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.|Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Kai
authors.initials: K
authors.lastname: Guo
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.|Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.|Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.|Okayama Medical Innovation Center, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.|Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Naijin
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.|Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.|Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Urology, Okamura Isshindow Hospital, Okayama, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kaku
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Abai
authors.initials: A
authors.lastname: Xu
authors.affiliation: Okayama Medical Innovation Center, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.affiliation: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.|Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.|Okayama Medical Innovation Center, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000008:administration & dosage*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D000077022:Survivin; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D007376:Interleukin-2; D009285:Naphthoquinones; D000077022:Survivin; C523798:sepantronium
keywords: IVIS; MDSCs; Treg; YM155; interleukin-2; renal cell carcinoma