Metabolomic analysis of uterine serous carcinoma with acquired resistance to paclitaxel.
Metabolomic analysis of uterine serous carcinoma with acquired resistance to paclitaxel.
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DOI：
10.18632/oncotarget.25868
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发表时间：
2018-08-10
期刊：
影响因子：
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通讯作者：
Nagase S
中科院分区：
文献类型：
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作者：
Seino M;Ohta T;Sugiyama A;Sakaki H;Sudo T;Tsutsumi S;Shigeta S;Tokunaga H;Toyoshima M;Yaegashi N;Nagase S
子宫浆液性癌（USC）比其他亚型的子宫内膜癌更具侵袭性，且预后不良。我们分析了对紫杉醇获得性耐药的USC的代谢组学特征。PTX-1细胞中谷胱甘肽（GSH）浓度高于USPC-1细胞。此外，USPC-1细胞中的GSH浓度在用紫杉醇处理后增加，但在PTX-1细胞中没有变化。PTX-1细胞中葡萄糖-6-磷酸（G6 P）和核糖-5-磷酸（R5 P）的浓度高于USPC-1细胞。紫杉醇处理后USPC-1细胞中的G6 P浓度不变，而PTX-1细胞中的G6 P浓度降低。我们的研究结果表明，GSH和葡萄糖代谢的增加可能与获得性耐药紫杉醇在USC，因此可能是抗USC治疗的目标。我们使用毛细管电泳CE-MS/MS系统比较了野生型USC细胞系（USPC-1）和PTX-1（一种来源于获得紫杉醇耐药的USPC-1的细胞系）中紫杉醇的代谢特征和反应。
Uterine serous carcinoma (USC) is more aggressive than other subtypes of endometrial carcinoma and is associated with a poor prognosis. We analyzed the metabolomic profile of USC with acquired resistance to paclitaxel. Glutathione (GSH) concentration in PTX-1 cells was higher than in USPC-1 cells. In addition, GSH concentration in the USPC-1 cells increased after treatment with paclitaxel but was unchanged in PTX-1 cells. Glucose-6-phosphate (G6P) and ribose-5-phosphate (R5P) concentrations in PTX-1 cells were higher than those in USPC-1 cells. G6P concentration in the USPC-1 cells was unchanged after treatment with paclitaxel, while it decreased in PTX-1 cells. Our results indicate that increased GSH and glucose metabolism may be related to acquiring resistance to paclitaxel in USC and thus may be targets for anti-USC therapy. We compared metabolic profiles and reactions to paclitaxel in both a wild type USC cell line (USPC-1) and PTX-1, a cell line derived from USPC-1 which acquired paclitaxel resistance, using a capillary electrophoresis CE-MS/MS system.