title: Chemoresistance of CD133(+) colon cancer may be related with increased survivin expression.
abstract: CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133(+) colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133(-) cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133(+) and siRNA-induced CD133(-) cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133(+) cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133(+) cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133(+) cells at 96 h after siRNA transfection. From this study, we conclude that CD133(+) cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133(+) colon cancer.
authors.affiliation: Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju, South Korea.
authors.forename: Mi-Ra
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju, South Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Ji
authors.affiliation: Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju, South Korea.
authors.forename: Khalilullah
authors.initials: K
authors.lastname: Mia-Jan
authors.affiliation: 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.forename: Mee-Yon
authors.initials: MY
authors.lastname: Cho
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D018938:Caco-2 Cells; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D000077022:Survivin; D015854:Up-Regulation
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; C107489:BIRC5 protein, human; D006023:Glycoproteins; D051034:Inhibitor of Apoptosis Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D034741:RNA, Small Interfering; D000077022:Survivin; D005472:Fluorouracil
keywords: CD133 protein; Cancer stem cell; Survivin; siRNA transfection