Özet:

Abstract Docetaxel is one of the most actively used chemotherapeutic agent in breast cancer which is the most frequent tumor in women. Recent studies propose that blocking the p53-MDM2 interaction may be effective in cancer treatment while the Sin3A mutation enhances cell proliferation in estrogen receptor (ER)-positive breast cancers. We aimed to investigate the effects of docetaxel on gene expression interactions and apoptosis in ER-positive breast cancer cell lines (MCF-7). MCF-7 cells were incubated for 24h with the treatment of escalating molar concentrations of docetaxel. The p53, MDM2 and Sin3A gene expression levels were measured by Real-Time PCR. The MTT assay was used to determine cellular viability. Apoptotic cells were detected by TUNEL. The mRNA expressions of p53, MDM2, and Sin3A increased in the same dose-dependent manner suggesting the highest effective level is 100nM docetaxel concentration (p<0.001). The p53 expression levels were strongly correlated with MDM2 (r=0.9379; p<10-7) and Sin3A (r=0.9965; p<10-13) in untreated, 10nM, 100nM and 1µM docetaxel concentrations. Cell viability of MCF-7 cells decreased dramatically in the 10µM and 100µM docetaxel treatments (p<0.001) and the IC50 value was 10µM. Apoptotic cell density was enhanced with the treatments of 10nM, 100nM, and 1µM docetaxel (p<0.001) in response to the gene expression levels. Our findings suggest that docetaxel directs the MCF-7 breast cancer cells to apoptosis in a dose-dependent manner and may thus further regulate the interaction of tumor suppressor p53 expression, protecting it from MDM2-mediated degradation and inhibiting Sin3A-mediated cell proliferation in compliance with the apoptotic cell density.

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