1Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
New Hearing Technologies Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Asian Pac J Cancer Prev. 2022 Mar 1;23(3):867-875. doi: 10.31557/APJCP.2022.23.3.867.
Atorvastatin is commonly used as a lipid lowering drug. The emerging interest in statins as anticancer agents is based on their pleiotropic effects on cancer cells. Among the statins, atorvastatin, and in cancers, breast malignancies have received less attention in preclinical investigations. In order to enhance the efficacy of cancer treatment, adjuvant, less expensive therapeutic strategies have been recently noticed. In this case, we investigated the in-vitro effect of atorvastatin on viability and migration of MCF7 breast cancer cell line.
We tested the cytotoxicity of atorvastatin on breast cancer cells survival by MTT assay. Annexin-V / PI staining and then flow cytometry of cancer cells in addition to quantitative real-time PCR tests quantified the apoptosis and necrosis of cancer cells. We figured out the impact of atorvastatin on cancer cell migration capability through scratch-wound healing assay and transwell migration examination. Inverted light microscope and fluorescent imaging displayed the morphological changes following treatment of MCF7 cells with atorvastatin.
We resulted that atorvastatin can trigger MCF7 cancer cells to undergo necrosis and caspase-dependent apoptosis based on the viable/dead cell number, mitotic cell cycle, gene expression, and morphological assays. The results were dose- and time-dependent and the half- maximal inhibitory concentration of atorvastatin for cancer cells' viability inhibition was 9.1 μM/L(nM/mL). Moreover, the migration of MCF7 cells were inhibited in the treated group as we figured out in two- and three-dimensional migration methods.
In-vitro inspection of drug-cancer cell interactions paves the way for future in-vivo research studies. These in-vitro results revealed that atorvastatin has anti-viability and anti-migration effects on breast cancer cells.
阿托伐他汀通常被用作降脂药物。他汀类药物作为抗癌药物的新兴趣基于它们对癌细胞的多效作用。在他汀类药物中,阿托伐他汀,以及在癌症中,乳腺癌在临床前研究中受到的关注较少。为了提高癌症治疗的疗效,最近人们注意到了辅助、更廉价的治疗策略。在这种情况下,我们研究了阿托伐他汀对 MCF7 乳腺癌细胞系活力和迁移的体外影响。
我们通过 MTT 测定法测试了阿托伐他汀对乳腺癌细胞存活的细胞毒性。通过流式细胞术定量分析 Annexin-V/PI 染色后,还定量实时 PCR 测试了癌细胞的凋亡和坏死。通过划痕愈合试验和 Transwell 迁移试验,我们研究了阿托伐他汀对癌细胞迁移能力的影响。倒置荧光显微镜和荧光成像显示了 MCF7 细胞用阿托伐他汀处理后的形态变化。
我们的结果表明,基于活/死细胞数量、有丝分裂细胞周期、基因表达和形态学测定,阿托伐他汀可引发 MCF7 癌细胞发生坏死和 caspase 依赖性细胞凋亡。结果呈剂量和时间依赖性,阿托伐他汀对癌细胞活力抑制的半最大抑制浓度为 9.1μM/L(nM/mL)。此外,我们在二维和三维迁移方法中发现,阿托伐他汀处理组 MCF7 细胞的迁移受到抑制。
药物-癌细胞相互作用的体外检测为未来的体内研究铺平了道路。这些体外结果表明,阿托伐他汀对乳腺癌细胞具有抗活力和抗迁移作用。