The effect of selective tyrosine kinase inhibitors on the expression of HIF1α and mTOR in p16-positive and -negative squamous cell carcinoma (HNSCC)

Background:

The impact of mTOR and HIF1α for local tumor progression and angiogenesis in HNSCC is essential. The present study analyzes the influence of selective tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib and gefitinib on the expression of HIF1α and mTOR in p16-positive and -negative squamous cell carcinoma in vitro.

Methods:

The expression of HIF1α and mTOR was measured and analyzed by using Enzyme linked immunosorbent assay (ELISA) in HNSCC 11A, HNSCC 14C and p16-positive CERV196 tumor cells after treatment with nilotinib, dasatinib, erlotinib and gefitinib (5 – 20 µmol/l, 24 – 96 hours of incubation) and compared to a chemonaive control.

Results:

All of the tested substances significantly reduced mTOR expression levels in all tested cell lines (< 0.05). There was no statistically significant difference with respect to the p16-status. HIF1α expression was reduced by all tested substances. However, a statistically significant increase of HIF1α was observed in p16-positive cells.

Discussion:

This is the first study to investigate the alteration of expression levels of HIF1α and mTOR under selective tyrosine kinase inhibition in both p16-positive and -negative squamous cell carcinomas. Our findings provide novel insights for a better understanding of HIF1α and mTOR and their interaction with selective small molecule inhibitors. The results reveal possible new approaches to discuss whether medical therapies in HNSCC could be supplemented with selective tyrosine kinase inhibitors in future.

Publication History

Publication Date:
18 April 2018 (online)