title: Induction of epithelial-mesenchymal transition and down-regulation of miR-200c and miR-141 in oxaliplatin-resistant colorectal cancer cells.
abstract: Epithelial-mesenchymal transition (EMT) and changes in the expression of the microRNA-200 (miR-200) family were examined in the human colorectal cancer (CRC) cell line SW620 with acquired oxaliplatin (L-OHP) resistance. Two CRC cell lines, SW480, derived from primary CRC, and SW620, derived from lymph node metastasis, which were obtained from the same patient, were used in the present study. L-OHP-resistant SW620 cells were obtained by exposure to L-OHP for 155 d. The concentration of L-OHP was increased to 80 µM in a stepwise manner. The IC50 value of L-OHP was increased 16-fold in L-OHP-resistant SW620 cells, which also displayed mesenchymal cell-like characteristics, such as the down-regulation of E-cadherin and up-regulation of vimentin. However, L-OHP-resistant SW480 cells were not obtained when the concentration of L-OHP was increased in a similar stepwise manner. The expression levels of members of the miR-200 family (miR-200a, miR-200b, miR-429, miR-200c, and miR-141) were significantly higher in SW480 cells than in SW620 cells. The expression levels of miR-200c and miR-141 were significantly lower in L-OHP-resistant SW620 cells than in control SW620 cells. L-OHP-resistant SW620 cells did not exhibit cross-resistance to other anti-cancer drugs used to treat CRC, such as 5-fluorouracil, irinotecan, and the active metabolite of irinotecan (SN-38). These results suggest that the down-regulated expression of miR-200c and miR-141 plays a role in selective resistance to L-OHP and EMT in CRC cells during repeated treatments with L-OHP.
authors.affiliation: Department of Pharmaceutics, Kobe Pharmaceutical University.
authors.forename: Shota
authors.initials: S
authors.lastname: Tanaka
authors.forename: Mika
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Wataru
authors.initials: W
authors.lastname: Hayashi
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ueda
authors.forename: Seigo
authors.initials: S
authors.lastname: Iwakawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000077150:Oxaliplatin; D014746:Vimentin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D014746:Vimentin; D000077150:Oxaliplatin