Authors: Poupak Fallahi Silvia Martina Ferrari Concettina La Motta Gabriele Materazzi Guido Bocci Federico Da Settimo Paolo Miccoli Alessandro Antonelli
Publish Date: 2015/08/19
Volume: 53, Issue: 1, Pages: 136-144
Abstract
We have studied the antitumor activity of two new “pyrazolo34dpyrimidine” compounds CLM29 and CLM24 that inhibit several targets including the RET tyrosine kinase epidermal growth factor receptor vascular endothelial growth factor receptor with an antiangiogenic effect in primary anaplastic thyroid cancer ATC cell cultures and in the human cell line 8305C undifferentiated thyroid cancer The antitumor effect of CLM29 and CLM24 was tested in nine primary ATC cultures obtained from patients at the time of surgery at the concentrations of 1 5 10 30 50 µM in 8305C cells at 1 5 10 30 50 µM for CLM29 and 0001 001 01 1 10 100 µM for CLM24 CLM29 and CLM24 significantly inhibited the proliferation of 8305C cells A significant reduction of proliferation with CLM29 and CLM24 in ATC cells P 001 for both ANOVA was shown CLM29 and CLM24 increased the percentage of apoptotic ATC cells dosedependently P 0001 ANOVA The V600E BRAF mutation was observed in three ATCs the results about the inhibition of proliferation by CLM29 and CLM24 obtained in ATC from tumors with V600E BRAF mutation were similar to those from tumors without BRAF mutation CLM29 inhibited migration and invasion P 001 of primary ATC cells while CLM24 had no significant effect The antitumor activity of two new “pyrazolo34dpyrimidine” compounds CLM24 CLM29 in vitro in ATC independent from BRAF mutation has been shown allowing a future clinical evaluation
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