Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.

Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.
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DOI:
10.3390/ijms140816600
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发表时间:
2013-08-12
影响因子:
5.6
通讯作者:
Madeddu R
Madeddu R
中科院分区:
生物学2区
文献类型:
--
作者:
Asara Y;Marchal JA;Carrasco E;Boulaiz H;Solinas G;Bandiera P;Garcia MA;Farace C;Montella A;Madeddu R

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工业化、工厂靠近城市以及人类工作活动导致过量使用含有重金属的物质,例如镉 (Cd),这可能对人类健康产生有害影响。镉的致癌作用及其与乳腺癌和其他肿瘤的关系已有报道。 5-氟尿嘧啶(5-FU)是一种氟嘧啶类抗癌药物,用于治疗结肠、乳腺癌、胃、肝脏和胰腺的实体瘤。本工作的目的是研究 Cd 对 5-FU 处理的 MCF-7 乳腺癌细胞的细胞周期、细胞凋亡以及基因和蛋白表达的影响。 Cd 改变了细胞周期特征,与单独使用 5-FU 相比,单独使用或与 5-FU 联合使用时其效果更大。 Cd 显着抑制用 5-FU 预处理的 MCF-7 细胞的凋亡。关于基因和蛋白质表达,bcl2 表达主要由所有涉及 Cd 的处理上调。大多数处理和所有时间的评估都降低了 caspase 8 和 caspase 9 的表达。所有涉及 Cd 的治疗,尤其是治疗半期时的 5-FU 加 Cd,C-myc 表达均增加。 Cd 加 5-FU 降低了细胞周期蛋白 D1 并增加了细胞周期蛋白 A1 的表达。总之,我们的结果表明,暴露于 Cd 会阻断 5-FU 在 MCF-7 细胞中的抗癌作用。这些结果可能对接受 5-FU 治疗且暴露于高水平镉的患者具有重要的临床意义。
Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.
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发表时间: 2009-12
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