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转染 p21 和 p53 肿瘤抑制质粒可抑制同源小鼠模型中的乳腺癌生长。

Transfection with p21 and p53 tumor suppressor plasmids suppressed breast tumor growth in syngeneic mouse model.

机构信息

Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia.

Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia.

出版信息

Gene. 2019 Jun 15;701:32-40. doi: 10.1016/j.gene.2019.02.082. Epub 2019 Mar 18.

Abstract

Treatment of breast cancer by delivering important tumor suppressor plasmids is a promising approach in the field of clinical medicine. We transfected p21 and p53 tumor suppressor plasmids, into different breast cancer cell lines using inorganic nanoparticles (NPs) of carbonate apatite to evaluate the effect of gene expression on reducing breast cancer cell growth. In triple negative MDA-MB-231 breast cancer cell line, the cytotoxicity assay upon combined delivery of p21 and p53 plasmid loaded NPs showed significant decrease in cell growth compared to distinct p21 or p53 treatments. Also, in MCF-7 and 4T1 cell lines, significant reduction in cellular growth was observed following p21 or p53 plasmid transfection. The Western blot data showed that NP loaded p21 and p53 transgene delivery in MDA-MB-231 cell line resulted in a noteworthy decrease in phosphorylated form of MAPK protein of MAPK/ERK pathway. The in vivo studies in syngeneic breast cancer mouse model demonstrated that the rate of growth and final tumor volume were reduced to a greater extent in mice that received intravenous injection of p21 + NP and p53 + NP therapeutics.

摘要

采用无机纳米碳酸钙载体制备肿瘤抑制质粒转染不同乳腺癌细胞系治疗乳腺癌是临床医学领域一种很有前途的方法。我们将 p21 和 p53 肿瘤抑制质粒转染到不同的乳腺癌细胞系中,采用无机纳米碳酸钙载体(NPs)评估基因表达对抑制乳腺癌细胞生长的效果。在三阴性 MDA-MB-231 乳腺癌细胞系中,与单独转染 p21 或 p53 质粒相比,联合转染 p21 和 p53 质粒负载 NPs 的细胞毒性试验显示细胞生长显著下降。此外,在 MCF-7 和 4T1 细胞系中,p21 或 p53 质粒转染后细胞生长均显著减少。Western blot 数据显示,MDA-MB-231 细胞系中负载 p21 和 p53 转染基因的 NPs 处理后,MAPK/ERK 通路中 MAPK 蛋白磷酸化形式明显减少。在同基因乳腺癌小鼠模型的体内研究中,接受 p21+NP 和 p53+NP 治疗的小鼠其肿瘤生长速度和最终肿瘤体积减小程度更大。

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