Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines
Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines
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DOI：
10.3892/ijo.2016.3558
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发表时间：
2016-08-01
影响因子：
5.2
通讯作者：
Calaf, Gloria M.
中科院分区：
文献类型：
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作者：
Pilco-Ferreto, Nesstor;Calaf, Gloria M.
乳腺癌是世界范围内女性死亡的主要原因之一，这是由于侵袭性行为、早期转移、对现有化疗剂的耐药性和高死亡率。阿霉素（Dox）是一种强有力的抗肿瘤药物。它是治疗乳腺癌最有效的药物之一。本研究的目的是评估Dox在乳腺癌细胞系MCF-10 F、MCF-7和MDA-MB-231中对凋亡和氧化应激的影响。这些研究表明，Dox降低抗凋亡Bcl-2蛋白的表达，并通过增加过氧化氢的产生，同时降低NF-κ B基因和蛋白在MCF-7（一种致瘤性三阳性细胞系）中的表达来影响氧化应激。Dox通过上调Bax、caspase-8和caspase-3蛋白表达，下调Bcl-2蛋白表达，诱导细胞凋亡。相反，在致瘤性三阴性乳腺癌细胞系MDA-MB-231中，通过增加SOD 2基因和蛋白表达以及过氧化氢产生来降低ROS损伤，同时NF-κ B蛋白表达降低。结论：Dox通过诱导Bcl-2家族和caspase蛋白水解过程激活细胞凋亡，同时通过影响ROS损伤降低MCF-7和MDA-MB-231细胞的氧化应激。
Breast cancer is one of the leading causes of mortality among women worldwide due to aggressive behavior, early metastasis, resistance to existing chemotherapeutic agent and high mortality rate. Doxorubicin (Dox) is a powerful anti tumoral drug. It is one of the most active agents for treatment of breast cancer. The aim of the present study was to evaluate the influence of Dox in apoptosis and oxidative stress in the breast cancer cell lines MCF-10F, MCF-7 and MDA-MB-231. These studies showed that Dox decreased anti-apoptotic Bcl-2 protein expression and affected oxidative stress by increasing hydrogen peroxide production and simultaneously decreasing NF-kappa B gene and protein expression in MCF-7, a tumorigenic triple-positive cell line. Results also indicated that Dox induced apoptosis by upregulating Bax, caspase-8 and caspase-3 and downregulation of Bcl-2 protein expression. On the contrary, ROS damage decreased by increasing SOD2 gene and protein expression and hydrogen peroxide production with parallel NF-kappa B protein expression decrease in MDA-MB-231, a tumorigenic triple-negative breast cancer cell line. It can be concluded that Dox activated apoptosis by inducing proteolytic processing of Bcl-2 family, caspases and simultaneously decreased oxidative stress by influencing ROS damage in MCF-7 and MDA-MB-231 cell lines.