mTOR- and tyrosine kinase inhibitors reduce AKT- and IGF-R expression in squamous cell carcinoma (HNSCC), dependent on p16 status

Background:

The activity of phosphor-AKT and IGF-R have a significant impact on tumour cell-proliferation, -metabolism and -growth. The present study investigates the influence of Dasatinib, Nilotinib, Gefitinib, Erlotinib as selective tyrosine kinase inhibitors as well as Everolimus as a mTOR Inhibitor on the expression of Phospho-AKT and IGF-R in p16-positive and -negative squamous cell carcinoma in vitro.

Methods:

Using ELISA the protein activity of the above-named receptors was measured in the HNSCC 11A, HNSCC 14C and the p16-negative cell line CERV196. The expression was measured after treatment with Nilotinib, Dasatinib, Erlotinib, Gefitinib and Everolimus (20 µmol/l, 24 – 96 hours of incubation) and compared to a chemo naive control.

Results:

All tested substances led to a significant reduction in Phospho-AKT and IGF-R expression in all tested cell lines (p < 0.05). In p16-positiv tumour cells the expression of Phospho-AKT was more significantly reduced than in p16-negative cells. Yet IGF-R expression was found to be reduced more in p16-negative cell lines.

Discussion:

This is the first study to investigate the alteration of expression levels of Phospho-AKT and IGF-R under selective tyrosine kinase inhibition in both p16-positive and -negative squamous cell carcinoma cell lines. The p16-status has significant impact on expression levels with the tested substances. P16-negative cells show a reduced angiogenesis effect through reduced expression of IGF-R, p16-positiv cells show reduced activity in the AKT-pathway. This leaves room for further studies to find more targeted therapy options with regard to HPV-status.

Publication History

Publication Date:
18 April 2018 (online)