Metabolomics profiling and chemoresistance mechanisms in ovarian cancer cell lines: Implications for targeting glutathione pathway

被引：1
|
作者：
Alarcon-Zapata, Pedro [1 ,2 ]
Perez, Andy J. [3 ]
Toledo-Onate, Karin [1 ]
Contreras, Hector [1 ]
Ormazabal, Valeska [4 ]
Nova-Lamperti, Estefania [1 ]
Aguayo, Claudio A. [1 ]
Salomon, Carlos [5 ]
Zuniga, Felipe A. [1 ]
机构：
[1] Univ Concepcion, Fac Pharm, Dept Clin Biochem & Immunol, Concepcion, Chile
[2] Univ Santo Tomas, Fac Ciencias, Dept Ciencias Basicas, Concepcion, Chile
[3] Univ Concepcion, Fac Pharm, Dept Instrumental Anal, Concepcion, Chile
[4] Univ Concepcion, Fac Biol Sci, Dept Pharmacol, Concepcion, Chile
[5] Univ Queensland, Ctr Clin Res, Royal Brisbane & Womens Hosp, Fac Med,Translat Extracellular Vesicles Obstet & G, Brisbane, Qld 4029, Australia
来源：
LIFE SCIENCES | 2023年 / 333卷
基金：
英国医学研究理事会;
关键词：
Ovarian cancer; Metabolomics; Chemoresistance; Glutathione; SK-OV-3; cells; LIPOSOMAL DOXORUBICIN; RECURRENT; CISPLATIN; CARBOPLATIN; SENSITIVITY; WOMEN; CHEMOTHERAPY; TOPOTECAN; DELIVERY; SPECTRA;
D O I：
10.1016/j.lfs.2023.122166
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Ovarian cancer presents a significant challenge due to its high rate of chemoresistance, which complicates the effectiveness of drug-response therapy. This study provides a comprehensive metabolomic analysis of ovarian cancer cell lines OVCAR-3 and SK-OV-3, characterizing their distinct metabolic landscapes. Metabolomics coupled with chemometric analysis enabled us to discriminate between the metabolic profiles of these two cell lines. The OVCAR-3 cells, which are sensitive to doxorubicin (DOX), exhibited a preference for biosynthetic pathways associated with cell proliferation. Conversely, DOX-resistant SK-OV-3 cells favored fatty acid oxidation for energy maintenance. Notably, a marked difference in glutathione (GSH) metabolism was observed between these cell lines. Our investigations further revealed that GSH depletion led to a profound change in drug sensitivity, inducing a shift from a cytostatic to a cytotoxic response. The results derived from this comprehensive metabolomic analysis offer potential targets for novel therapeutic strategies to overcome drug resistance. Our study suggests that targeting the GSH pathway could potentially enhance chemotherapy's efficacy in treating ovarian cancer.
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页数：12
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