title: ERCC1 expression and chemosensitivity in uterine cervical adenocarcinoma cells.
abstract: BACKGROUD/AIM: We previously demonstrated that high protein expression of excision repair cross-complementation group-1 (ERCC1) was associated with poor disease-free survival in patients who received adjuvant cisplatin-based chemotherapy or chemoradiotherapy with cisplatin, and was shown to be an independent prognostic factor. In the present study, we evaluated ERCC1 expression levels in uterine cervical adenocarcinoma cell lines to assess whether they are affected by treatment with cisplatin with and without 5-fluorouracil (5-FU).
  
  
  METHODS
  Firstly, half-maximal (50%) inhibitory concentration (IC50) values for cisplatin or 5-FU were calculated in cervical adenocarcinoma, HCA-1, and TCO-2 cell lines by 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, yellow tetrazole (MTT) assay. ERCC1 mRNA and protein levels were investigated by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Secondly, cisplatin-resistant HCA-1 cells, designated HCA-1R cells were established, and IC50 values for cisplatin and 5-FU were calculated by the MTT assay. ERCC1 mRNA expression levels were investigated using quantitative RT-PCR following treatment with cisplatin with and without 5-FU.
  
  
  RESULTS
  HCA-1 and TCO-2 cells exhibited similar sensitivity to cisplatin, and 5-FU, and comparable expression of ERCC1 mRNA and protein levels. HCA-1R cells exhibited two-fold higher resistance to cisplatin and a significantly higher level of ERCC1 mRNA expression compared to native HCA-1 cells. ERCC1 expression was significantly elevated by cisplatin treatment, which was reduced by co-administration of 5-FU in HCA-1, TCO-2 and HCA-1R cells.
  
  
  CONCLUSIONS
  The current study demonstrated an association between ERCC1 expression and sensitivity to cisplatin in cervical adenocarcinoma cells. Co-administration of cisplatin and 5-FU revealed synergistic or additive effects through inhibition of ERCC1 expression in cervical adenocarcinoma cells. Therefore, it is possible that a combination therapy of cisplatin and 5-FU or 5-FU derivatives constitutes an ideal treatment regimen, from the ERCC1 inhibition point of view in cervical adenocarcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, Banbuntane Hotokukai Hospital, Fujita Health University, 3-6-10 Otobashi, Nakagawa-ku, Nagoya, Aichi, 454-8509, Japan. khase@fujita-hu.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Torii
authors.forename: Rina
authors.initials: R
authors.lastname: Kato
authors.forename: Yukito
authors.initials: Y
authors.lastname: Minami
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Takuma
authors.initials: T
authors.lastname: Fujii
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Udagawa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D005472:Fluorouracil
keywords: 5-FU; Cervical adenocarcinoma; ERCC1; HCA-1; HCA-1R cells; TCO-2; chemosensitivity; cisplatin