Sato Seiya, Itamochi Hiroaki, Kigawa Junzo, Oishi Tetsuro, Shimada Muneaki, Sato Shinya, Naniwa Jun, Uegaki Kazunori, Nonaka Michiko, Terakawa Naoki
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.
Cancer Sci. 2009 Mar;100(3):546-51. doi: 10.1111/j.1349-7006.2008.01065.x. Epub 2008 Dec 19.
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.
卵巢黏液性腺癌对紫杉醇和卡铂标准化疗的耐药与预后不良相关，因此需要有效的治疗方法。本研究旨在确定一种针对卵巢黏液性腺癌的有效化疗方案。本研究使用了五种人卵巢黏液性腺癌细胞系（MN-1、OMC-1、RMUG-L、RMUG-S、TU-OM-1）。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法测定细胞对抗癌药物的敏感性，并通过计算每种药物的曲线下面积来评估药物敏感性。通过蛋白质印迹分析确认蛋白质表达。我们还在裸鼠异种移植模型中研究了联合化疗对生存的疗效。抗癌药物的半数抑制浓度（IC50）范围广泛。曲线下面积表明，五个细胞系中的两个（MN-1、TU-OM-1）对奥沙利铂、5-氟尿嘧啶和依托泊苷敏感，只有一个（TU-OM-1）对喜树碱的活性代谢物7-乙基-10-羟基喜树碱敏感。所有细胞系对顺铂和紫杉醇均耐药。奥沙利铂和5-氟尿嘧啶联合使用对所有细胞系产生相加或协同作用。奥沙利铂和5-氟尿嘧啶联合使用显著延长了裸鼠卵巢黏液性腺癌异种移植模型的生存期。奥沙利铂敏感细胞系中切除修复交叉互补组1的蛋白质表达水平较低。暴露于5-氟尿嘧啶会下调卵巢黏液性腺癌细胞中交叉互补组1的表达。我们得出结论，由奥沙利铂和5-氟尿嘧啶组成的联合化疗是治疗卵巢黏液性腺癌的有效方法，可能是一种新治疗策略的关键候选方案。
