Tyrosinkinaseinhibitors in HPV-positive and -negative SCC induce apoptotic Parameters

Introduction:

Targeted tumor therapy gives hope for improved prognosis in head and neck cancer. Tyrosinkinaseinhibitors influence cellular signaling cascades of cancer cells in many different ways. A desirable result would be induction of apoptosis.

Methods:

This in vitro-study evaluated expression of Fas-ligand, Fas and caspase 3 by ELISA under erlotinib, gefitinib, dasatinib, nilotinib and everolimus at 5, 10 and 20µmol/ml in two p16-negative and a p16-positive squamous cell carcinoma cell line. Incubation time was 1 – 4 days. Expression was compared to a chemonaive control.

Results:

Target proteins were expressed in all three cell lines. For caspase 3 and Fas-ligand especially dasatinib and erlotinib led to a significant reduction of expression. Nilotinib, everolimus and less marked gefitinib caused significant Caspase-3-induction with the exception of UMSCC 14C cells. Nilotinib, everolimus and gefitinib induced the expression of Fas-ligand but not significant in all cases. Effects on Fas were heterogeneous. All applied agents reduced expression in UMSCC 11A cells significantly compared to negative control. Dasatinib and erlotinib produced equal results in UMSCC 14C. For cell line p16-positive CERV196 all drugs induced Fas-expression compared to the negative control, and only dasatinib did not reach a significant effect.

Conclusion:

Significant induction of apoptotic signals was shown for nilotinib, everolimus and gefitinib. Fas-expression was mostly suppressed in p16-negative cells but p16-positive CERV196 cells showed increased Fas-levels compared to chemonaive control. Proliferation assays could reveal consequences for cell survival in further studies.

Publication History

Publication Date:
18 April 2018 (online)