Abstract

IntroductionUterine 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.ResultsGlutathione (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.ConclusionOur 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 MethodsWe 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.

Highlights

  • Uterine serous carcinoma (USC) is more aggressive than other subtypes of endometrial carcinoma and is associated with a poor prognosis

  • Our results indicate that increased GSH and glucose metabolism may be related to acquiring resistance to paclitaxel in USC and may be targets for anti-USC therapy

  • We first confirmed resistance to paclitaxel in USPC-1 and PTX-1 cells and found that PTX-1 cells were significantly resistant to paclitaxel compared to USPC-1 cells (Figure 1)

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Summary

Introduction

Uterine serous carcinoma (USC) is more aggressive than other subtypes of endometrial carcinoma and is associated with a poor prognosis. Most endometrial cancers are classified as early stage and low grade (i.e., endometrioid carcinoma grade 1, 2), with a 5-year survival of greater than 85% [1]. The rare histologic type uterine serous carcinoma (USC) is more aggressive than other subtypes and is associated with a poor prognosis. The proportion of USC is less than 10% of all subtypes of endometrial carcinoma, but the 5-year survival of USC is poor with only 18–27%, compared to that of low-grade types [1,2,3]. Type I endometrial carcinomas comprise endometrioid carcinomas (grade 1, 2), are usually seen in younger patients, and are associated with obesity, hyperlipidemia, and hyperestrogenism. Type II endometrial carcinomas include serous carcinoma and clear cell carcinoma, are seen in older patients, and are not associated with hormonal factors

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