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.

Advanced Ovarian Cancer: Primary or Interval Debulking? Five Categories of Patients in View of the Results of Randomized Trials and Tumor Biology: Primary Debulking Surgery and Interval Debulking Surgery for Advanced Ovarian Cancer

“…The authors concluded that NACT-IDS appears to increase the risk for platinum resistance [55]. Drug resistance after NACT correlates with in vitro drug resistance [56][57][58][59]. A second possible explanation for why NACT-IDS has not been able to further improve OS might be the violation of the dose-density effect by the interruption of chemotherapy with IDS [60].…”

Mucinous but not clear cell histology is associated with inferior survival in patients with advanced stage ovarian carcinoma treated with platinum‐paclitaxel chemotherapy

“…17 Preclinical data have suggested a synergism of oxaliplatin and 5-fluorouracil in cisplatin-resistant experimental models. 18 This synergism results from down-regulation of the excision-repair cross-complementation group 1 by 5-fluorouracil, resulting in enhanced sensitivity to oxaliplatin. Furthermore, irinotecan, another effective agent in gastrointestinal malignancies, has been used in small series for the treatment of these tumors with encouraging results.…”

Cetuximab inhibits the growth of mucinous ovarian carcinoma tumor cells lacking KRAS gene mutations

“…The 5 MAC cell lines used in this study (RMUG-L, RMUG-S, MN-1, OMC-1 and MCAS) (21)(22)(23)(24)(25) , 100 U/ml penicillin, and 100 µg/ml streptomycin (Gibco) at 37˚C in a 5% CO 2 atmosphere for no longer than 8 weeks after recovery from frozen stocks.…”