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The Role of the LY294002 - A Non-Selective Inhibitor of Phosphatidylinositol 3-Kinase (PI3K) Pathway- in Cell
Andressa Duarte1, Giórgia Gobbi Silveira1,2, Danilo Figueiredo Soave1,3
1Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Brazil.
Abstract:
The activation of PI3K further activates subsequent regulatory pathways, which are activated via AKT phosphorylation. AKT is closely related to the Bcl-2 family, a protein known to be involved in cell survival. AKT also has a relationship with inflammatory and glycolytic mediators. The present work aimed to evaluate the relationship between the PI3K/AKT pathway, cell survival/proliferation, inflammatory mediators and the glycolytic pathway in oral squamous cell carcinoma. All experiments were performed in the SCC25 oral squamous cell carcinoma cell line. In the presence or absence of PI3K pathway inhibitors, we analyzed the protein expression of pAKT and AKT; X-linked inhibitor of apoptosis protein; Bcl-2-associated death promoter; Bcl-2-like protein two inhibitor; cyclooxygenase 1; cyclooxygenase-2; and glycoprotein-associated glucose transporter 1. For the functional characterization of treated or untreated cells, we also performed matrix invasion assays, cell migration assays, and cell proliferation assays. Our results demonstrated that activation of the PI3K/AKT pathway is directly related to members of the Bcl-2 family and GLUT1, but not the inflammatory mediators COX1 and COX2. Our data suggest that the PI3K/AKT pathway is related to cell survival and proliferation in oral squamous cell carcinoma through its interaction with Bcl-2 family members.
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Insights
The PI3K/AKT pathway promotes oral cancer cell survival and proliferation by interacting with Bcl-2 family proteins, but not inflammatory mediators like COX1 and COX2.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The phosphoinositide 3-kinase (PI3K)/AKT pathway regulates crucial cellular processes.
- AKT interacts with the Bcl-2 family, influencing cell survival, and with inflammatory and glycolytic mediators.
Purpose of the Study:
- To investigate the relationship between the PI3K/AKT pathway, cell survival/proliferation, inflammatory mediators, and the glycolytic pathway in oral squamous cell carcinoma (OSCC).
Main Methods:
- Experiments were conducted on the SCC25 OSCC cell line.
- Protein expression of pAKT, AKT, Bcl-2 family members, COX1, COX2, and GLUT1 was analyzed with and without PI3K inhibitors.
- Functional assays included matrix invasion, cell migration, and cell proliferation.
Main Results:
- PI3K/AKT pathway activation correlated with Bcl-2 family members and GLUT1 expression.
- No direct relationship was observed between the PI3K/AKT pathway and inflammatory mediators COX1 and COX2.
- The PI3K/AKT pathway was linked to cell survival and proliferation.
Conclusions:
- The PI3K/AKT pathway significantly contributes to oral squamous cell carcinoma cell survival and proliferation.
- This pathway's effect on OSCC is mediated through its interaction with Bcl-2 family proteins.
- The PI3K/AKT pathway's role in OSCC does not appear to involve inflammatory mediators COX1 and COX2.
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