Influence of Tyrosine Kinase Inhibitors and Everolimus on TGFβ1 and TGF-β Receptor 2 in Squamous Cell Carcinoma Cells

Background/Aim: Transforming growth factor-beta(TGF-beta) plays a significant role in the formation of differentcancer subtypes. There is evidence that TGF-beta pathwayspromote cancerogenic cell characteristics but also have tumor-suppressor capabilities. The tyrosine kinase inhibitors nilotinib,dasatinib, erlotinib, gefitinib, and everolimus are approved astargeted therapies for several tumor entities, including head andneck squamous cell carcinoma (HNSCC). This study aimed toinvestigate the effects of these substances on the expressionlevels of TGF beta 1 and TGF-beta receptor type 2 (TGF beta R2) in HPV-negative and HPV-positive SCC cell cultures. Materials andMethods: Expression patterns of TGF beta 1 and TGF beta R2 weredetermined using enzyme-linked immunosorbent assay (ELISA)in three HNSCC cell lines (i.e., HNSCC-11A, HNSCC-14C, andCERV196). These cells were incubated with nilotinib, dasatinib,erlotinib, gefitinib, and everolimus (20 mu mol/l) and comparedto a chemonaive control. An assessment of concentration levelswas conducted after 24, 48, 72, and 96 h of treatment. Results:Statistically significant changes in the expression levels ofTGF beta 1 and TGF beta R2 were found in all tested cell cultures(p<0.05) compared to the negative control. An increase inTGF beta-R2 expression was detected after treatment with most ofthe tested tyrosine kinase inhibitors, whereas a reduction in TGF beta 1 was observed. The addition of everolimus had theopposite effect on both TGF beta R2 and TGF-B1- expression.Conclusion: Expression of TGF beta 1 and TGF beta R2 was detectedin all cultured HNSCC cell lines. Nilotinib, dasatinib, erlotinib,gefitinib, and everolimus had an impact on the expression levelsof TGF beta 1 and TGF beta R2 in vitro.