Open Access

Olaparib promotes FABP4 expression and reduces antitumor effect in ovarian cancer cells with a BRCA1 mutation

  • Authors:
    • Wei Huang
    • Hongxue Meng
    • Ye Xu
    • Lan Huang
    • Ge Lou
  • View Affiliations

  • Published online on: November 20, 2024     https://doi.org/10.3892/ol.2024.14813
  • Article Number: 67
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Olaparib (AZD2281) is used as a first‑line maintenance treatment for patients with ovarian cancer (OC) with a breast cancer susceptibility gene (BRCA) mutation. Fatty acid binding protein 4 (FABP4) may serve an important role in cancer, but its role in olaparib‑treated OC with a BRCA mutation requires further clarification. To explore the function of FABP4 and enhance the efficacy of AZD2281 in OC, cell counting kit‑8, cell apoptosis, cell cycle, colony formation, cell transfection, western blotting, reverse transcription‑quantitative polymerase chain reaction, chromatin immunoprecipitation, seahorse and reactive oxygen species assays were performed. In the present study, AZD2281 significantly promoted cell apoptosis, and inhibited cell cycle progression and colony formation in COV362 cells. In addition, AZD2281 significantly upregulated the levels of CCAAT enhancer binding protein α (CEBPα), peroxisome proliferator activated receptor γ (PPARγ) and FABP4. AZD2281 markedly promoted fold enrichment of CEBPα in the promoters of PPARγ and FABP4. Furthermore, FABP4 overexpression significantly decreased cell apoptosis and promoted cell cycle progression and colony formation. In contrast, FABP4 knockdown demonstrated the opposite effects. In addition, FABP4 significantly regulated levels of reactive oxygen species, adenosine triphosphate, aerobic glycolysis, basal respiration rate and fatty acid oxidation. The combination of AZD2281 with the FABP4 inhibitor BM S309403 further significantly increased cell apoptosis and decreased colony formation. In conclusion, the findings of the present study demonstrated that AZD2281 significantly enhanced FABP4 expression, leading to diminished antitumor efficacy in OC cells with a BRCA mutation by regulating CEBPα‑PPARγ. Conversely, the combination of AZD2281 and FABP4 inhibitor BM S309403 demonstrated heightened antitumor effectiveness, presenting a promising therapeutic strategy for treating patients with OC with a BRCA mutation.
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Copy and paste a formatted citation
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Spandidos Publications style
Huang W, Meng H, Xu Y, Huang L and Lou G: Olaparib promotes FABP4 expression and reduces antitumor effect in ovarian cancer cells with a <em>BRCA1</em> mutation. Oncol Lett 29: 67, 2025.
APA
Huang, W., Meng, H., Xu, Y., Huang, L., & Lou, G. (2025). Olaparib promotes FABP4 expression and reduces antitumor effect in ovarian cancer cells with a <em>BRCA1</em> mutation. Oncology Letters, 29, 67. https://doi.org/10.3892/ol.2024.14813
MLA
Huang, W., Meng, H., Xu, Y., Huang, L., Lou, G."Olaparib promotes FABP4 expression and reduces antitumor effect in ovarian cancer cells with a <em>BRCA1</em> mutation". Oncology Letters 29.2 (2025): 67.
Chicago
Huang, W., Meng, H., Xu, Y., Huang, L., Lou, G."Olaparib promotes FABP4 expression and reduces antitumor effect in ovarian cancer cells with a <em>BRCA1</em> mutation". Oncology Letters 29, no. 2 (2025): 67. https://doi.org/10.3892/ol.2024.14813