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Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway

by Kasamatsu, Atsushi , Nozaki, Ryunosuke , Ando, Toshiaki , Nobuchi, Takafumi , Kawasaki, Kohei , Uzawa, Katsuhiro , Iyoda, Manabu , Saito, Tomoaki

in AKT protein / Apoptosis / Cancer therapies / Caspase-3 / Cell growth / Cell viability / Chemoresistance / Chemotherapy / Cisplatin / Drug dosages / Experiments / Extracellular signal-regulated kinase / Ginkgolides / Intracellular / Intracellular signalling / Medical prognosis / Oral carcinoma / Oral squamous cell carcinoma / Patients / Phosphorylation / Platelet-activating factor / Proteins / Signal transduction / Therapeutic applications / Therapeutic targets / Tumors / Variance analysis

2021

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Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway

by Kasamatsu, Atsushi , Nozaki, Ryunosuke , Ando, Toshiaki , Nobuchi, Takafumi , Kawasaki, Kohei , Uzawa, Katsuhiro , Iyoda, Manabu , Saito, Tomoaki

2021

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Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway

by Kasamatsu, Atsushi , Nozaki, Ryunosuke , Ando, Toshiaki , Nobuchi, Takafumi , Kawasaki, Kohei , Uzawa, Katsuhiro , Iyoda, Manabu , Saito, Tomoaki

2021

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Journal Article

Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway

Kasamatsu, Atsushi,

Nozaki, Ryunosuke,

Ando, Toshiaki,

Nobuchi, Takafumi,

Kawasaki, Kohei,

Uzawa, Katsuhiro,

Iyoda, Manabu,

Saito, Tomoaki

2021

Overview

The platelet-activating factor receptor (PAFR) is a key molecule that participates in intracellular signaling pathways, including regulating the activation of kinases. It is involved in cancer progression, but the detailed mechanism of its chemosensitivity is unknown. The purpose of the current study was to elucidate the mechanism regulating cisplatin (CDDP) sensitivity through PAFR functions in oral squamous cell carcinoma (OSCC). We first analyzed the correlation between PAFR expression and CDDP sensitivity in seven OSCC-derived cell lines based upon cell viability assays. Among them, we isolated 2 CDDP-resistant cell lines (Ca9-22 and Ho-1-N-1). In addition to conducting PAFR-knockdown (si ) experiments, we found that ginkgolide B (GB), a specific inhibitor of PAFR, enhanced both CDDP chemosusceptibility and apoptosis. We next evaluated the downstream signaling pathway of PAFR in si -treated cells and GB-treated cells after CDDP treatment. In both cases, we observed decreased phosphorylation of ERK and Akt and increased expression of cleaved caspase-3. These results suggest that PAFR is a therapeutic target for modulating CDDP sensitivity in OSCC cells. Thus, GB may be a novel drug that could enhance combination chemotherapy with CDDP for OSCC patients.

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MDPI AG

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