Romanian Society of Pharmaceutical Sciences

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CELL AND DOSE-DEPENDENT ATTENUATION OF ATORVASTATIN ON LPS-ASSOCIATED TNF-α EXPRESSION AND THE ASSOCIATED TUMOR GROWTH INDUCTION IN BREAST CANCER CELLS

NADA ALMUTAIRI, NOJOOD ALTWAIJRY, SEEMA ZARGAR *

Department of Biochemistry, College of Science, King Saud University, PO Box 22452, Riyadh 11451, Saudi Arabia

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Chronic inflammation contributes to breast cancer progression through cytokine effects on tumor growth. Tumor necrosis factor-alpha (TNF-α) is a key inflammatory mediator implicated in breast cancer subtypes. Atorvastatin (ATO), beyond its lipid-lowering effects, has been reported to exert anti-inflammatory and anti-tumor properties. We investigated the effects of the ATO on TNF-α expression, secretion, and growth in MCF-7 and MDA-MB-231 breast cancer cells in response to lipopolysaccharide (LPS) stimulation. Treatments used were LPS 10 µg/mL and ATO (0 - 9 µM), alone or combined. The antiproliferative effects of ATO were assessed by MTT and RTCA analysis. TNF-α mRNA expression and secretion levels were quantified by qPCR using TaqMan probes and by a Luminex immunoassay. ATO reduced the LPS-induced cell proliferation. ATO also lowered TNF-α gene expression relative to LPS-treated cells, although LPS-induced upregulation of TNF-α expression in MCF-7 cells did not reach statistical significance. In MDA-MB-231 cells, the effects of ATO were less pronounced, supporting a cell type- and dose-dependent pleiotropic anti-inflammatory action of ATO in breast cancer.