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

Kohei Kawasaki1, Atsushi Kasamatsu2, Toshiaki Ando1

  • 1Department of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670, Japan.

Cancers
|December 24, 2021
PubMed

Insights

Platelet-activating factor receptor (PAFR) inhibition enhances cisplatin sensitivity in oral cancer. Ginkgolide B, a PAFR inhibitor, boosts chemotherapy effectiveness by promoting apoptosis and reducing key signaling proteins.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Platelet-activating factor receptor (PAFR) plays a role in cancer progression, but its precise mechanism in chemosensitivity remains unclear.
  • Understanding PAFR's function is crucial for developing targeted therapies in oral squamous cell carcinoma (OSCC).

Purpose of the Study:

  • To investigate the role of PAFR in regulating cisplatin (CDDP) sensitivity in OSCC.
  • To elucidate the downstream signaling pathways affected by PAFR inhibition in CDDP-treated OSCC cells.

Main Methods:

  • Cell viability assays were used to assess CDDP sensitivity in OSCC cell lines with varying PAFR expression.
  • PAFR was inhibited using knockdown (siPAFR) and a specific inhibitor, ginkgolide B (GB).
  • Downstream signaling pathways (ERK, Akt, cleaved caspase-3) were analyzed following CDDP treatment in inhibited cells.

Main Results:

  • Two CDDP-resistant OSCC cell lines (Ca9-22 and Ho-1-N-1) were identified.
  • PAFR knockdown and GB treatment significantly enhanced CDDP chemosusceptibility and induced apoptosis.
  • Inhibition of PAFR led to decreased phosphorylation of ERK and Akt, and increased cleaved caspase-3 expression.

Conclusions:

  • PAFR acts as a therapeutic target for overcoming CDDP resistance in OSCC.
  • Ginkgolide B shows potential as a novel agent to enhance combination chemotherapy with CDDP for OSCC patients.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.0K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.0K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.1K
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
13.9K