The Role of the LY294002 - A Non-Selective Inhibitor of Phosphatidylinositol 3-Kinase (PI3K) Pathway- in Cell Survival and Proliferation in Cell Line SCC-25.

Andressa Duarte,Giórgia Gobbi Silveira,Alfredo Ribeiro Silva,Danilo Figueiredo Soave,João Paulo Oliveira Costa

doi:10.31557/apjcp.2019.20.11.3377

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.

Highlights

Cancer is a public health problem, with 21.4 million new cases and 13.2 million deaths estimated to occur in 2030 (Ferlay et al, 2015)
Our results demonstrated that activation of the Phosphatidylinositol 3-Kinase (PI3K)/AKT pathway is directly related to members of the Bcl-2 family and glucose transporter 1 (GLUT1), but not the inflammatory mediators COX1 and COX2
We demonstrated that, in SCC-25 oral squamous cell carcinoma cells, the PI3K pathway and the proteins COX1 and COX2 have no direct relation (Figure 2)

Summary

Introduction

Cancer is a public health problem, with 21.4 million new cases and 13.2 million deaths estimated to occur in 2030 (Ferlay et al, 2015). The PI3K (phosphatidylinositide 3-kinase)/AKT (protein kinase B) signaling pathway has been shown to be involved in many types of cancer in humans, with a role in the development of tumors and in the potential response of the tumor to the treatment. The first protein described as the target of AKT protein kinase was glycogen synthase kinase 3 (GSK-3), an important enzyme involved in glycogen metabolism (Cross et al, 1995). Several other proteins have been described as targets for phosphorylation and consequent activation or inhibition by AKT, including anti-apoptotic and pro-apoptotic proteins such as the X-linked apoptosis inhibitor (XIAP) (Dan et al, 2004) and BCL-2 associated death promoter (BAD) (Harada et al, 2001). With regards to inflammatory mediators, the PI3K/AKT pathway is directly related to several inflammatory diseases (Chen et al, 2016)

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