title: The small molecule survivin inhibitor YM155 may be an effective treatment modality for colon cancer through increasing apoptosis.
abstract: Survivin has a known beneficial role in the survival of both cancer cells and normal cells. Therapies targeting survivin have been proposed as an alternative treatment modality for various tumors; however, finding the proper indication for this toxic therapy is critical for reducing unavoidable side effects. We recently observed that high survivin expression in CD133(+) cells is related to chemoresistance in Caco-2 colon cancer cells. However, the effect of survivin-targeted therapy on CD133(+) colon cancer is unknown. In this study, we investigated the roles of CD133 and survivin expression in colon cancer biology in vitro and comparatively analyzed the anticancer effects of survivin inhibitor on CD133(+) cells (ctrl-siRNA group) and small interfering RNA (siRNA)-induced CD133(-) cells (CD133-siRNA group) obtained from a single colon cancer cell line. CD133 knockdown via siRNA transfection did not change the tumorigenicity of cells, although in vitro survivin expression levels in CD133(+) cells were higher than those in siRNA-induced CD133(-) cells. The transfection procedure seemed to induce survivin expression. Notably, a significant number of CD133(-) cells (33.8%) was found in the cell colonies of the CD133-siRNA group. In the cell proliferation assay after treatment, YM155 and a combination of YM155 and 5-fluorouracil (5-FU) proved to be far more effective than 5-FU alone. A significantly increased level of apoptosis was observed with increasing doses of YM155 in all groups. However, significant differences in therapeutic effect and apoptosis among the mock, ctrl-siRNA, and CD133-siRNA groups were not detected. Survivin inhibitor is an effective treatment modality for colon cancer; however, the role of CD133 and the use of survivin expression as a biomarker for this targeted therapy must be verified.
authors: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, South Korea. Electronic address: lvvlchina@msn.cn.
authors: Wan Lu
authors: WL
authors: Li
authors: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, South Korea. Electronic address: mira1125@yonsei.ac.kr.
authors: Mi-Ra
authors: MR
authors: Lee
authors: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, South Korea; Institute of Genomic Cohort, Yonsei University Wonju College of Medicine, Wonju, South Korea. Electronic address: meeyon@yonsei.ac.kr.
authors: Mee-Yon
authors: MY
authors: Cho
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009285:Naphthoquinones / Q000008:administration & dosage*; D000077022:Survivin; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D000077022:Survivin; C523798:sepantronium
keywords: Apoptosis; CD133 protein; Colon cancer; Survivin; YM155