CC BY-NC-ND 4.0 · Laryngorhinootologie 2018; 97(S 02): S105
DOI: 10.1055/s-0038-1640075
Abstracts
Onkologie: Oncology

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

B Kuhlin
1   Hals-Nasen-Ohrenklinik UMM Mannheim, Mannheim
,
B Kramer
2   HNO Klinik UMM Mannheim, Mannheim
,
N Rotter
2   HNO Klinik UMM Mannheim, Mannheim
,
C Aderhold
2   HNO Klinik UMM Mannheim, Mannheim
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    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.


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    No conflict of interest has been declared by the author(s).

    Dr. med. Beatrice Kuhlin
    UMM Mannheim,
    Theodor-Kutzer-Ufer 1 – 3, 68167,
    Mannheim

    Publication History

    Publication Date:
    18 April 2018 (online)

    © 2018. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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