ArticleJournal of hematology & oncology2014
Synergistic effects of combined platelet-activating factor receptor and epidermal growth factor receptor targeting in ovarian cancer cells.
Article in Journal of hematology & oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Impact of the crosstalk between the PTEN and PAFR as well as PAFR and EGFR pathways in cancer.Exploration of drug science · 2025Article
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- Platelet-Activating Factor Acetylhydrolase Expression in BRCA1 Mutant Ovarian Cancer as a Protective Factor and Potential Negative Regulator of the Wnt Signaling Pathway.Biomedicines · 2021Article
- Expression and pharmacological inhibition of TrkB and EGFR in glioblastoma.Molecular biology reports · 2020Article
- Platelet-activating factor induces the stemness of ovarian cancer cells via the PAF/PAFR signaling pathway.American journal of translational research · 2020Article
- Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy.Clinics (Sao Paulo, Brazil) · 2018Review
- In vivo RNAi screening identifiesBlood advances · 2018Article
- Platelet-Activating Factor Receptor Ligands Protect Tumor Cells from Radiation-Induced Cell Death.Frontiers in oncology · 2018Article
- CCR9 in cancer: oncogenic role and therapeutic targeting.Journal of hematology & oncology · 2016Review
- Ezrin Enhances EGFR Signaling and Modulates Erlotinib Sensitivity in Non-Small Cell Lung Cancer Cells.Neoplasia (New York, N.Y.) · 2016Article
- Knockdown of protein phosphatase 5 inhibits ovarian cancer growthOncology letters · 2016Article
- Transactivation of epidermal growth factor receptor through platelet-activating factor/receptor in ovarian cancer cells.Journal of experimental & clinical cancer research : CR · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic alterations, including the overexpression of epidermal growth factor receptor (EGFR), play a crucial role in ovarian carcinogenesis. To date, EGFR targeting has shown limited antitumor effects in ovarian cancer when administered as monotherapy. We previously identified platelet-activating factor receptor (PAFR) as being overexpressed in ovarian cancer and found that its ligand PAF evoked EGFR phosphorylation. To determine whether PAFR targeting can enhance the antitumor efficacy of EGFR inhibition, we investigated the effects of a PAFR antagonist (WEB2086) in conjunction with an EGFR inhibitor (AG1478).
methodsThe expression of EGFR and PAFR in CAOV-3 and SKOV-3 ovarian cancer cell lines was measured by Western blot and immunocytochemistry. Synergy was determined using isobologram analysis. The effects of combined PAFR and EGFR targeting on both cells were assessed by using CCK-8, transwell, flow cytometry, western blot analysis. In vivo studies were conducted using CAOV-3 cells xenografted in nu/nu mice.
resultsTreatment with combination WEB2086 and AG1478 resulted in significantly greater inhibition of proliferation and invasion compared to either drug alone. When examining equipotent combinations of WEB2086 and AG1478 to determine potential synergy, a combination index (CI) of 0.49 was identified for CAOV-3 cells and a CI of 0.58 for SKOV-3 cells indicating synergy. This co-inhibition induced significantly more apoptosis and arrested the cells at G0/G1 phase in both cell lines. The activation of PAFR and/or EGFR induced phosphorylation of the mTOR, AKT, and MAPK pathways. Combined PAFR and EGFR targeting synergistically diminished the expression of PAFR and EGFR phosphorylation and downstream signaling. In vivo studies further verified the antitumor effects of combined PAFR and EGFR targeting in a CAOV-3 xenograft model.
conclusionsThese results suggest that WEB2086 and AG1478 are synergistic in ovarian cancer cells with high expression of both PAFR and EGFR. The presented approach may have important therapeutic implications in the treatment of ovarian cancer patients.
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