Cytotoxic Effect of Combination Treatment of Vitamin D and Pitavastatin on the MCF7 Breast Cancer Cells

Sanaa Al Tawil, Mohamed Abdelrhman Adris Abdulla, S. Aliwaini
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Abstract

Breast cancer is the most common cancer among women. Several common approaches to cancer management are being used, but many cancer patients develop resistance to chemotherapy drugs. Here we describe the antiproliferative effect of the combination of vitamin D and pitavastatin against breast cancer cells. Aims: To determine the combined cytotoxic effect of both vitamin D and pitavastatin on the MCF7 breast cancer cell line and to study the mechanism of action behind this effect. Methods: In vitro experimental study using the MCF7 estrogen receptor-positive breast cancer cells. The effective doses of the combinations were determined by MTT, and western blotting was used to determine the different protein levels. Results: The 50% inhibitory concentrations (IC50s) of vitamin D and pitavastatin on MCF7 cells were 5.1 μM and 5.5 μM, respectively. However, when the cells were pre-treated with a low dose of vitamin D (1μM) the new pitavastatin IC50 was 1.1 μM. In addition, the combined treatment inhibited the phosphorylation of STAT3 protein in MCF7 cells and increased p53 and p21 protein levels. Conclusion: The combination of pitavastatin and vitamin D showed a synergistic cytotoxic effect by inducing cell cycle arrest and apoptosis.
维生素D联合匹伐他汀对MCF7乳腺癌细胞的细胞毒性作用
乳腺癌是女性中最常见的癌症。目前正在使用几种常见的癌症治疗方法,但许多癌症患者对化疗药物产生了耐药性。在这里,我们描述了维生素D和匹伐他汀对乳腺癌细胞的抗增殖作用。目的:观察维生素D和匹伐他汀对MCF7乳腺癌细胞系的联合细胞毒作用,并探讨其作用机制。方法:采用MCF7雌激素受体阳性乳腺癌细胞进行体外实验研究。MTT法测定组合有效剂量,western blotting法测定不同蛋白水平。结果:维生素D和匹伐他汀对MCF7细胞的50%抑制浓度(ic50)分别为5.1 μM和5.5 μM。然而,当细胞用低剂量的维生素D (1μM)预处理时,新的匹伐他汀IC50为1.1 μM。此外,联合治疗抑制了MCF7细胞中STAT3蛋白的磷酸化,增加了p53和p21蛋白水平。结论:匹伐他汀与维生素D联用具有协同细胞毒作用,可诱导细胞周期阻滞和细胞凋亡。
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