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体外评价亲脂性纳米铋(BisBAL NPs)对乳腺癌细胞的抗肿瘤作用。

In vitro evaluation of the antitumor effect of bismuth lipophilic nanoparticles (BisBAL NPs) on breast cancer cells.

机构信息

Universidad Autónoma de Nuevo León, UANL, Facultad de Odontología, Laboratorio de Biología Molecular, Monterrey, Nuevo León, México,

Subdirección de Investigación Básica, Instituto Nacional de Cancerología, CDMX, México.

出版信息

Int J Nanomedicine. 2018 Oct 5;13:6089-6097. doi: 10.2147/IJN.S179095. eCollection 2018.

Abstract

AIM

The objective of this study was to evaluate the antitumor activity of lipophilic bismuth nanoparticles (BisBAL NPs) on breast cancer cells.

MATERIALS AND METHODS

The effect of varying concentrations of BisBAL NPs was evaluated on human MCF-7 breast cancer cells and on MCF-10A fibrocystic mammary epitheliocytes as noncancer control cells. Cell viability was evaluated with the MTT assay, plasma membrane integrity was analyzed with the calcein AM assay, genotoxicity with the comet assay, and apoptosis with the Annexin V/7-AAD assay.

RESULTS

BisBAL NPs were spherical in shape (average diameter, 28 nm) and agglomerated into dense electronic clusters. BisBAL NP induced a dose-dependent growth inhibition. Most importantly, growth inhibition was higher for MCF-7 cells than for MCF-10A cells. At 1 µM BisBAL NP, MCF-7 growth inhibition was 51%, while it was 11% for MCF-10A; at 25 µM BisBAL NP, the growth inhibition was 81% for MCF-7 and 24% for MCF-10A. With respect to mechanisms of action, a 24-hour exposure of 10 and 100 µM BisBAL NP caused loss of cell membrane integrity and fragmentation of tumor cell DNA. BisBAL NPs at 10 µM were genotoxic to and caused apoptosis of breast cancer cells.

CONCLUSION

BisBAL NP-induced growth inhibition is dose dependent, and breast cancer cells are more vulnerable than noncancer breast cells. The mechanism of action of BisBAL NPs may include loss of plasma membrane integrity and a genotoxic effect on the genomic DNA of breast cancer cells.

摘要

目的

本研究旨在评估亲脂性铋纳米粒子(BisBAL NPs)对乳腺癌细胞的抗肿瘤活性。

材料与方法

评估不同浓度 BisBAL NPs 对人 MCF-7 乳腺癌细胞和 MCF-10A 纤维囊性乳腺上皮细胞(非癌细胞对照)的影响。用 MTT 法评估细胞活力,用 calcein AM 法分析质膜完整性,用彗星试验评估遗传毒性,用 Annexin V/7-AAD 试验评估细胞凋亡。

结果

BisBAL NPs 呈球形(平均直径 28nm),聚集形成密集的电子簇。BisBAL NP 诱导剂量依赖性生长抑制。最重要的是,MCF-7 细胞的生长抑制作用高于 MCF-10A 细胞。在 1μM BisBAL NP 时,MCF-7 细胞的生长抑制率为 51%,而 MCF-10A 细胞为 11%;在 25μM BisBAL NP 时,MCF-7 细胞的生长抑制率为 81%,而 MCF-10A 细胞为 24%。就作用机制而言,10 和 100μM BisBAL NP 暴露 24 小时会导致质膜完整性丧失和肿瘤细胞 DNA 片段化。BisBAL NPs 浓度为 10μM 时对乳腺癌细胞具有遗传毒性并诱导其凋亡。

结论

BisBAL NP 诱导的生长抑制作用呈剂量依赖性,乳腺癌细胞比非癌细胞更敏感。BisBAL NPs 的作用机制可能包括质膜完整性丧失和对乳腺癌细胞基因组 DNA 的遗传毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb8d/6179729/b54296ac600f/ijn-13-6089Fig1.jpg

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