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人乳腺癌的p53基因治疗:使用转铁蛋白修饰的二氧化硅纳米颗粒

p53 gene therapy of human breast carcinoma: using a transferrin-modified silica nanoparticles.

作者信息

Rejeeth Chandrababu, Kannan Soundrapandian

机构信息

Proteomics and Molecular Cell Physiology Lab, Department of Zoology, School of Life Sciences, Bharathiar University, Coimbatore, 641 046, Tamil Nadu, India.

出版信息

Breast Cancer. 2016 Jan;23(1):101-110. doi: 10.1007/s12282-014-0537-z. Epub 2014 May 4.

Abstract

BACKGROUND

Nanoparticles have an enormous potential for development in biomedical applications, such as gene or drug delivery. In our study, we examined the efficacy of p53 gene therapy in human breast carcinoma (MCF-7) cells using silica nanoparticles (SiNPs) supplemented with transferrin.

METHODS

MCF-7 cells were exposed to transferrin-SiNPs-p53 in vitro, and the growth inhibition rate, expression of p53 and bax, and induction of apoptosis were measured 48 h later.

RESULTS

Treatment of MCF-7 cells with transferrin-SiNPs-p53 resulted in 60.7 % growth inhibition. Wild-type p53 expression and an increase in bax expression were observed following transfection with transferrin-SiNPs-p53, and 20.5 % of the treated MCF-7 cells were apoptotic. In vivo, the MCF-7 tumor transplanted into nude mice grew to 5-6 mm in diameter. Following growth of the tumor to this size, transferrin-SiNPs-p53 was locally applied to the peripheral tumor (day 0) and then applied once every 5 days for a total of six times. During the administration period, tumor growth did not occur, and the mean tumor volume on the last day of administration (day 25) was 10.0 % of that in the saline control group.

CONCLUSION

These results suggest that p53 gene therapy via transferrin-modified silica nanoparticles is an effective strategy for treatment of breast carcinoma.

摘要

背景

纳米颗粒在生物医学应用(如基因或药物递送)中具有巨大的发展潜力。在我们的研究中,我们使用补充了转铁蛋白的二氧化硅纳米颗粒(SiNPs)检测了p53基因疗法对人乳腺癌(MCF-7)细胞的疗效。

方法

将MCF-7细胞在体外暴露于转铁蛋白-SiNPs-p53,48小时后测量生长抑制率、p53和bax的表达以及凋亡诱导情况。

结果

用转铁蛋白-SiNPs-p53处理MCF-7细胞导致60.7%的生长抑制。在用转铁蛋白-SiNPs-p53转染后观察到野生型p53表达和bax表达增加,并且20.5%的经处理的MCF-7细胞发生凋亡。在体内,移植到裸鼠体内的MCF-7肿瘤直径长到5-6毫米。在肿瘤生长到这个大小时,将转铁蛋白-SiNPs-p53局部应用于肿瘤周边(第0天),然后每5天应用一次,共应用六次。在给药期间,肿瘤没有生长,给药最后一天(第25天)的平均肿瘤体积是生理盐水对照组的10.0%。

结论

这些结果表明,通过转铁蛋白修饰的二氧化硅纳米颗粒进行p53基因治疗是治疗乳腺癌的一种有效策略。

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