对获得性紫杉醇耐药的子宫浆液性癌的代谢组学分析。

Metabolomic analysis of uterine serous carcinoma with acquired resistance to paclitaxel.

作者信息

Seino Manabu, Ohta Tsuyoshi, Sugiyama Akiko, Sakaki Hirotsugu, Sudo Takeshi, Tsutsumi Seiji, Shigeta Shogo, Tokunaga Hideki, Toyoshima Masafumi, Yaegashi Nobuo, Nagase Satoru

机构信息

Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Iidanishi, Yamagata 990-9585, Japan.

Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Iidanishi, Yamagata 990-9585, Japan.

出版信息

Oncotarget. 2018 Aug 10;9(62):31985-31998. doi: 10.18632/oncotarget.25868.

INTRODUCTION

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.

RESULTS

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.

CONCLUSION

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.

MATERIALS AND METHODS

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.

引言

子宫浆液性癌（USC）比子宫内膜癌的其他亚型更具侵袭性，且预后较差。我们分析了对紫杉醇产生获得性耐药的子宫浆液性癌的代谢组学特征。

结果

PTX - 1细胞中的谷胱甘肽（GSH）浓度高于USPC - 1细胞。此外，用紫杉醇处理后，USPC - 1细胞中的GSH浓度增加，但PTX - 1细胞中的GSH浓度未发生变化。PTX - 1细胞中的6 - 磷酸葡萄糖（G6P）和5 - 磷酸核糖（R5P）浓度高于USPC - 1细胞。用紫杉醇处理后，USPC - 1细胞中的G6P浓度未发生变化，而PTX - 1细胞中的G6P浓度降低。