Karaciğer ve Meme Kanseri Hücreleri ile Embriyonik Böbrek Hücrelerinde Doksorubisinin Apoptotik Genlerin ve Mdr-1 Geninin Ekspresyon Düzeylerine Etkisi

Abstract

In this study, in order to investigate roles of certain genes and expression levels of these genes in apoptosis, MCF-7 (breast), HEPG2 (liver) cancer cells and HEK293 embryonic kidney cells were treated with increasing doses of Doxorubicin (DOX). It was examined whether these cells have single nucleotide polymorphism on codon 72 of the most important gene of apoptotic pathway, p53 and Arg/Pro heterozygote form is detected in all the cells. Later, expression levels of TP53, MDM2, BCL-2, BAX and MDR-1 measured. According to the results, expression level of TP53 was increased in low doses and decreased in higher doses of the drug in MCF-7 and HEPG2 cells. In HEK293 cells, it was decreased in dose-independent manner. The expression level of MDM2 was significantly decreased in MCF-7 cells when they were treated with 400 and 800 nM DOX; while it was increased in lower doses and decreased in higher doses in HEPG2 and HEK293 cells. The expression level of BCL-2 was decreased in MCF-7 and HEK293 cells independently from the applied doses. In HEPG2 it was increased with the exposure of 50 nM dose of drug and decreased with the higher doses. The expression level of BAX was increased in lower doses and decreased in higher doses in MCF-7 cells. In HEPG2 cells, it was increased with 50 nM dose of drug and remained unchanged in higher doses when compared to the control. The expression of MDR-1 is decreased in MCF-7 cells when compared to the control, remained relatively unchanged in HEPG2 cells and increased in HEK293 cells with increasing doses of the drug. Thus it was demonstrated that these three cells lines have different apoptosis and multiple drug resistance profiles.