Abstract | OBJECTIVE: DESIGN: MATERIALS, SETTING, METHODS: Immunohistochemistry, ELISA, and mass spectrometry methods were used to measure the level of ceramides, C1P, and CerK in primary tissues. Proliferation and apoptosis assays were performed in ovarian cancer cells after CERK depletion, CERK overexpression, and NVP-231 treatment in the absence or presence of cisplatin. RESULTS: Compared to normal ovarian cells, CerK and its mediating bioactive sphingolipids ceramide and C1P were decreased in ovarian cancer tissues. Interestingly, cisplatin-resistant ovarian cancer cells displayed increased CerK, decreased ceramide, and increased C1P, and furthermore, that CerK level was closely associated with ceramide and C1P levels in ovarian cancer cells. Functional analysis demonstrated that CerK overexpression was sufficient to promote growth and confer chemoresistance in ovarian cancer cells. CerK inhibition via both genetic and pharmacological approaches suppressed growth and induced apoptosis in cisplatin-resistant cells, and furthermore, this significantly augmented cisplatin's efficacy. LIMITATIONS: The functional analysis of C1P was performed on in vitro ovarian cancer cells. In vivo studies were needed to further confirm the effects of CERK inhibition. CONCLUSIONS: Our work is the first to show the critical role of CerK as the underlying mechanism of ovarian cancer chemoresistance, through regulating ceramide and C1P.
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Authors | Jing Zou, Long Jian |
Journal | Gynecologic and obstetric investigation
(Gynecol Obstet Invest)
Vol. 88
Issue 1
Pg. 61-70
( 2023)
ISSN: 1423-002X [Electronic] Switzerland |
PMID | 36682357
(Publication Type: Journal Article)
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Copyright | © 2023 S. Karger AG, Basel. |
Chemical References |
- ceramide 1-phosphate
- Cisplatin
- ceramide kinase
- Ceramides
- Sphingolipids
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Topics |
- Humans
- Female
- Cisplatin
(pharmacology)
- Ovarian Neoplasms
(drug therapy)
- Ceramides
(metabolism, pharmacology)
- Sphingolipids
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