ANTITUMOR ANTI-EGFR ACTION OF A NEW DERIVATIVE OF 9-DIHYDROACRIDONE

Abstract

The basis of modern strategies for the treatment of oncological diseases is the use of pharmaceutical products. A high frequency of refractoriness and formation of tumor cells' resistance to anti-EGFR drugs dictates the need to develop new active inhibitors of this intracellular kinase. The aim of this work was to study the antitumor effect of a new compound – a derivative of 9-Dihydroacridone on in vitro models of EGFR-expressing tumor cells. Material and methods. The compound of 9-aminium-3,3-dimethyl-3,4-dihydroacridine-1(2H)-one L-2-hydroxy-butandiovate (laboratory cipher of the developer institution LHT-17-19) was studied. Three cultures of human stomach cancer were used for the study. The analysis of tumor cell growth suppression was performed in a test with 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide, intracellular identification of the phosphorylated form of receptor tyrosine kinase – by Western blotting. Study results. The compound of 9-dihydroacridone dose-dependently suppresses the growth of EGFR-expressing tumor cells of human gastric cancer. Hs746T culture cells have the greatest sensitivity to the compound, MKN1 has the least. The antitumor activity of the substance is based on the ability to reduce the intracellular pool of the activated form of receptor tyrosine kinase EGFR. Conclusions. The obtained results allow enable to consider the compound LHT-17-19 as a promising compound for the subsequent preclinical study of its antitumor properties in animal systems.