Abstract
BACKGROUND: Breast cancer is one of the most common malignancies and causes of mortality in women. Combination therapies are one of the treatment approaches that contribute to better performance, reduced dosage, and drug resistance. Hydralazine is an antihypertensive drug, but it can induce epigenetic changes such as DNA methylation reversal in cancer cells. ATRA is a type of vitamin A, and its deficiency is associated with the progression of various diseases. It can bind to receptors and regulate genes to inhibit multiple types of cancers. METHODS: According to bioinformatics studies, combining these two drugs can inhibit breast cancer cells. This study investigates various biological pathways, such as HIF-1, VEGF, and WNT, with the key genes of CCND1, VEGFA, VEGFA2, HIF1A, and HIF1A-AS. In the laboratory, MDA-MB-231, as a tumor cell line, and MCF10, as a normal cell line, were cultured, and the MTT assay was performed to obtain the IC(50) of the drugs. Using these concentrations, isobologram and wound healing tests were performed. Gene expression was measured using real-time PCR. RESULTS: Results showed that hydralazine alone stimulated cancer cell growth, potentially inducing breast cancer. ATRA reduced cell survival in both normal and cancer cells. However, the combination treatment exhibited differential effects, causing a significant reduction in survival in cancer cells while the impact on normal cells was not significant. CONCLUSIONS: Hydralazine/ATRA combination inhibits cancer cell proliferation and their adaptation to hypoxia. These findings suggest a potential for new treatment targeting breast cancer cells with minimized side effects. CLINICAL TRIAL REGISTRATION: Clinical trial number: "not applicable".