Investigation of the Cell Stabilization and the Epithelial to Mesenchymal Transition Effect of Flavopiridol in Mouse Lung Squamous Cell Carcinoma

Abstract

Abstract Background: Lung malignancy is a leading cause of cancer related morbidity and mortality worldwide. The three main subtypes of Non-small cell lung cancer (NSCLC) are adenocarcinoma, squamous cell lung cancers (SqCLCs) and large-cell carcinoma. Flavopiridol is a flavone that inhibits several cyclindependent kinases and exhibits potent growthinhibitory activity, apoptosis and G1 phase arrest in a number of human tumor cell lines. The present study focused on the effect of flavopiridol in cell stabilization, cell adhesion, junctional complex and epithelial to mesenchymal transition (EMT) in mouse lung squamous cell carcinoma cell. Methods: Cell viability and proliferation of untreated controls and flavopiridol treated cells were determined by using the WST-1 assay. SqCLCs and M. dunni mouse skin fibroblast cells (MSF) cells immunofluorescence analyses were performed for the evaluation of Hsp90β, e-cadherin and occludin. The percentages of CD133+/CD44+ cells in the flavopiridol treated cells when compared with the control untreated cells by flow cytometric analysis. Results: Flow cytometric analysis showed that the percentages of CD133+ and CD44+ cells did not show significant changes when compared to the untreated cells. Hsp90b expression which is significantly available in SqCLCs was considered as important its significant reduction by following flavopiridol application and also flavopiridol caused the significant increase the E-cadherin expression but there was no significant effect on the occludin expression. SqCLCs cells are uniformly highly sensitive to flavopiridol induced cytotoxicity during prolonged 72 h exposure to clinically achievable concentrations of this drug. Conclusions: These observations may have translational implications for the use of flavopiridol in the treatment of SqCLCs.