title: Combination chemotherapy of oxaliplatin and 5-fluorouracil may be an effective regimen for mucinous adenocarcinoma of the ovary: a potential treatment strategy.
abstract: Resistance of ovarian mucinous adenocarcinoma to standard chemotherapy with paclitaxel and carboplatin is associated with poor prognosis, and an effective treatment is needed. The present study aimed to identify an effective chemotherapy for ovarian mucinous adenocarcinoma. Five human ovarian mucinous adenocarcinoma cell lines (MN-1, OMC-1, RMUG-L, RMUG-S, TU-OM-1) were used in this study. Sensitivity of the cells to the anticancer agents was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and we assessed drug sensitivity by calculating the assay area under the curve for each agent. Protein expression was confirmed by Western blot analysis. We also examined the efficacy of combination chemotherapy on survival in a xenograft model of nude mice. The IC(50) to anticancer agents ranged widely. The assay area under the curve indicated that two of five cell lines (MN-1, TU-OM-1) were sensitive to oxaliplatin, 5-fluorouracil and etoposide, and only one (TU-OM-1) was sensitive to 7-ethyl-10-hydroxycamptothecin, which is an active metabolite of camptothecin. All cell lines were resistant to cisplatin and paclitaxel. The combination of oxaliplatin and 5-fluorouracil resulted in additive or synergistic effects on all cell lines. The combination of oxaliplatin and 5-fluorouracil significantly prolonged survival in a ovarian mucinous adenocarcinoma xenograft model of nude mice. Protein expression levels of the excision repair cross-complementation group 1 were lower in oxaliplatin sensitive cell lines. Exposure to 5-fluorouracil down-regulated cross-complementation group 1 expression in ovarian mucinous adenocarcinoma cells. We conclude that combination chemotherapy consisting of oxaliplatin and 5-fluorouracil was an effective treatment for ovarian mucinous adenocarcinoma and may be a pivotal candidate for a novel treatment strategy.
authors.affiliation: Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Sato
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itamochi
authors.forename: Junzo
authors.initials: J
authors.lastname: Kigawa
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Oishi
authors.forename: Muneaki
authors.initials: M
authors.lastname: Shimada
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.forename: Jun
authors.initials: J
authors.lastname: Naniwa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Uegaki
authors.forename: Michiko
authors.initials: M
authors.lastname: Nonaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Terakawa
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000187:drug effects; D004720:Endonucleases / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D000077150:Oxaliplatin; D023041:Xenograft Model Antitumor Assays
chemical_list: D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D005472:Fluorouracil