Abstract | BACKGROUND: METHODS: The upregulation of PAFR in CDDP-treated ovarian cancer cells was observed using realtime PCR and Western blot. The potential role of PAFR in modulating the CDDP sensitivity was assessed using a pharmacological inhibitor and siRNA knockdown. The PAFR-activated signalling pathways involved in cell responses to CDDP were assessed. RESULTS:
Cisplatin induced increased PAFR expression in two ovarian cancer cell lines. The upregulation of PAFR by CDDP correlated with the time-dependent accumulation of NF-κB and HIF-1α in the nucleus. The inhibition of PAFR sensitised the ovarian cancer cells to CDDP. The PI3K and ERK pathways lie downstream of activated PAFR in CDDP-treated cells and their inhibition enhanced CDDP sensitivity. Finally, co-treatment with a PAFR antagonist ( Ginkgolide B) and CDDP markedly reduced tumour growth in an in vivo model of ovarian cancer. CONCLUSIONS: Together, these findings suggest that PAFR is a novel and promising therapeutic target for sensitising ovarian cancer cells to CDDP.
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Authors | Y Yu, X Zhang, S Hong, M Zhang, Q Cai, M Zhang, W Jiang, C Xu |
Journal | British journal of cancer
(Br J Cancer)
Vol. 111
Issue 3
Pg. 515-24
(Jul 29 2014)
ISSN: 1532-1827 [Electronic] England |
PMID | 24921917
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Azepines
- HIF1A protein, human
- Hypoxia-Inducible Factor 1, alpha Subunit
- Platelet Membrane Glycoproteins
- RELA protein, human
- Receptors, G-Protein-Coupled
- Transcription Factor RelA
- Triazoles
- platelet activating factor receptor
- WEB 2086
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Azepines
(pharmacology)
- Cell Line, Tumor
- Cell Nucleus
(metabolism)
- Cisplatin
(pharmacology)
- Combined Modality Therapy
- Drug Resistance, Neoplasm
- Female
- Gene Expression
(drug effects)
- Gene Knockdown Techniques
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
(metabolism)
- MAP Kinase Signaling System
- Mice, Nude
- Ovarian Neoplasms
(drug therapy, metabolism)
- Platelet Membrane Glycoproteins
(antagonists & inhibitors, genetics, metabolism)
- Protein Transport
- Receptors, G-Protein-Coupled
(antagonists & inhibitors, genetics, metabolism)
- Transcription Factor RelA
(metabolism)
- Triazoles
(pharmacology)
- Tumor Burden
(drug effects)
- Xenograft Model Antitumor Assays
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