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用银纳米颗粒处理的人肝癌细胞HepG2的mRNA转录组分析

mRNA transcriptome profiling of human hepatocellular carcinoma cells HepG2 treated with -silver nanoparticles.

作者信息

Azhar Nur Asna, Abu Bakar Siti Aishah, Citartan Marimuthu, Ahmad Nor Hazwani

机构信息

Department of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas 13200, Pulau Pinang, Malaysia.

Liver Malignancies Research Program, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas 13200, Pulau Pinang, Malaysia.

出版信息

World J Hepatol. 2023 Mar 27;15(3):393-409. doi: 10.4254/wjh.v15.i3.393.

Abstract

BACKGROUND

The demand for the development of cancer nanomedicine has increased due to its great therapeutic value that can overcome the limitations of conventional cancer therapy. However, the presence of various bioactive compounds in crude plant extracts used for the synthesis of silver nanoparticles (AgNPs) makes its precise mechanisms of action unclear.

AIM

To assessed the mRNA transcriptome profiling of human HepG2 cells exposed to G. Don ()AgNPs.

METHODS

The proliferative activity of hepatocellular carcinoma (HepG2) and normal human liver (THLE3) cells treated with AgNPs were measured using MTT assay. The RNA samples were extracted and sequenced using BGIseq500 platform. This is followed by data filtering, mapping, gene expression analysis, differentially expression genes analysis, Gene Ontology analysis, and pathway analysis.

RESULTS

The mean IC values of AgNPs on HepG2 was 4.38 ± 1.59 μg/mL while on THLE3 cells was 800 ± 1.55 μg/mL. Transcriptome profiling revealed an alteration of 296 genes. AgNPs induced the expression of stress-associated genes such as , and . Cellular signalling pathways were potentially activated through MAPK, TNF and TGF pathways that are responsible for apoptosis and cell cycle arrest. The alteration of , indicated the uptake of -AgNPs both clathrin-dependent and clathrin-independent endocytosis.

CONCLUSION

This study provides new insights into gene expression study of biosynthesised AgNPs on cancer cells. The cytotoxicity effect is mediated by the aberrant gene alteration, and more interestingly the unique selective antiproliferative properties indicate the AgNPs as an ideal anticancer candidate.

摘要

背景

癌症纳米药物的开发需求不断增加,因为其具有巨大的治疗价值,能够克服传统癌症治疗的局限性。然而,用于合成银纳米颗粒(AgNPs)的植物粗提物中存在各种生物活性化合物,这使得其确切作用机制尚不清楚。

目的

评估暴露于G. Don ()AgNPs的人HepG2细胞的mRNA转录组谱。

方法

使用MTT法测量用AgNPs处理的肝癌(HepG2)和正常人肝脏(THLE3)细胞的增殖活性。提取RNA样本并使用BGIseq500平台进行测序。随后进行数据过滤、映射、基因表达分析、差异表达基因分析、基因本体分析和通路分析。

结果

AgNPs对HepG2的平均IC值为4.38±1.59μg/mL,而对THLE3细胞的平均IC值为800±1.55μg/mL。转录组分析显示296个基因发生改变。AgNPs诱导了与应激相关的基因如、和的表达。细胞信号通路可能通过负责细胞凋亡和细胞周期停滞的MAPK、TNF和TGF通路被激活。、的改变表明-AgNPs通过网格蛋白依赖和非依赖的内吞作用被摄取。

结论

本研究为生物合成的AgNPs对癌细胞的基因表达研究提供了新的见解。细胞毒性作用是由异常的基因改变介导的,更有趣的是,独特的选择性抗增殖特性表明AgNPs是一种理想的抗癌候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/444c/10075008/1072cbc6f76e/WJH-15-393-g001.jpg

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