In vivo detection of dysregulated choline metabolism in paclitaxel-resistant ovarian cancers with proton magnetic resonance spectroscopy

التفاصيل البيبلوغرافية
العنوان: In vivo detection of dysregulated choline metabolism in paclitaxel-resistant ovarian cancers with proton magnetic resonance spectroscopy
المؤلفون: Jing Lu, Ying Li, Yong Ai Li, Li Wang, An Rong Zeng, Xiao Liang Ma, Jin Wei Qiang
المصدر: Journal of Translational Medicine. 20
بيانات النشر: Springer Science and Business Media LLC, 2022.
سنة النشر: 2022
مصطلحات موضوعية: Ovarian Neoplasms, Mice, Paclitaxel, Phospholipases, Phosphorylcholine, Proton Magnetic Resonance Spectroscopy, Animals, Humans, Female, General Medicine, General Biochemistry, Genetics and Molecular Biology, Choline
الوصف: Background Chemoresistance gradually develops during treatment of epithelial ovarian cancer (EOC). Metabolic alterations, especially in vivo easily detectable metabolites in paclitaxel (PTX)-resistant EOC remain unclear. Methods Xenograft models of the PTX-sensitive and PTX-resistant EOCs were built. Using a combination of in vivo proton-magnetic resonance spectroscopy (1H-MRS), metabolomics and proteomics, we investigated the in vivo metabolites and dysregulated metabolic pathways in the PTX-resistant EOC. Furthermore, we analyzed the RNA expression to validate the key enzymes in the dysregulated metabolic pathway. Results On in vivo 1H-MRS, the ratio of (glycerophosphocholine + phosphocholine) to (creatine + phosphocreatine) ((GPC + PC) to (Cr + PCr))(i.e. Cho/Cr) in the PTX-resistant tumors (1.64 [0.69, 4.18]) was significantly higher than that in the PTX-sensitive tumors (0.33 [0.10, 1.13]) (P = 0.04). Forty-five ex vivo metabolites were identified to be significantly different between the PTX-sensitive and PTX-resistant tumors, with the majority involved of lipids and lipid-like molecules. Spearman’s correlation coefficient analysis indicated in vivo and ex vivo metabolic characteristics were highly consistent, exhibiting the highest positive correlation between in vivo GPC + PC and ex vivo GPC (r = 0.885, P P 1H-MRS. Conclusions These findings suggested that dysregulated choline metabolism was associated with PTX-resistance in EOCs and the elevated tCho on in vivo 1H-MRS could be as an indicator for the PTX-resistance in EOCs.
تدمد: 1479-5876
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7be2e25a8598d1341986219e5a7ccb60
https://doi.org/10.1186/s12967-022-03292-z
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....7be2e25a8598d1341986219e5a7ccb60
قاعدة البيانات: OpenAIRE