LC-MS Based Sphingolipidomic Study on A2780 Human Ovarian Cancer Cell Line and its Taxol-resistant Strain

Drug resistance elicited by cancer cells continue to cause huge problems world-wide, for example, tens of thousands of patients are suffering from taxol-resistant human ovarian cancer. However, its biochemical mechanisms remain unclear. Sphingolipid metabolic dysregulation has been increasingly rega...

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Bibliographic Details
Published in:Scientific reports 2016-10, Vol.6 (1), p.34684-34684, Article 34684
Main Authors: Huang, Hao, Tong, Tian-Tian, Yau, Lee-Fong, Chen, Cheng-Yu, Mi, Jia-Ning, Wang, Jing-Rong, Jiang, Zhi-Hong
Format: Article
Language:English
Subjects:
631/67/2327
631/92/608
Cell Line, Tumor
Chromatography, Liquid - methods
Drug resistance
Drug Resistance, Neoplasm
Female
Humanities and Social Sciences
Humans
Lipid metabolism
Metabolism
multidisciplinary
Multivariate analysis
Ovarian cancer
Ovarian Neoplasms - metabolism
Paclitaxel
Paclitaxel - pharmacology
Science
Sphingolipids
Sphingolipids - analysis
Sphingomyelin
Studies
Tandem Mass Spectrometry - methods
Tumor cell lines
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Summary:Drug resistance elicited by cancer cells continue to cause huge problems world-wide, for example, tens of thousands of patients are suffering from taxol-resistant human ovarian cancer. However, its biochemical mechanisms remain unclear. Sphingolipid metabolic dysregulation has been increasingly regarded as one of the drug-resistant mechanisms for various cancers, which in turn provides potential targets for overcoming the resistance. In the current study, a well-established LC-MS based sphingolipidomic approach was applied to investigate the sphingolipid metabolism of A2780 and taxol-resistant A2780 (A2780T) human ovarian cancer cell lines. 102 sphingolipids (SPLs) were identified based on accurate mass and characteristic fragment ions, among which 12 species have not been reported previously. 89 were further quantitatively analyzed by using multiple reaction monitoring technique. Multivariate analysis revealed that the levels of 52 sphingolipids significantly altered in A2780T cells comparing to those of A2780 cells. These alterations revealed an overall increase of sphingomyelin levels and significant decrease of ceramides, hexosylceramides and lactosylceramides, which concomitantly indicated a deviated SPL metabolism in A2780T. This is the most comprehensive sphingolipidomic analysis of A2780 and A2780T, which investigated significantly changed sphingolipid profile in taxol-resistant cancer cells. The aberrant sphingolipid metabolism in A2780T could be one of the mechanisms of taxol-resistance.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep34684