外体
血管生成
微泡
流式细胞术
细胞周期
A549电池
活力测定
癌症研究
细胞生长
生物
细胞生物学
细胞
化学
分子生物学
小RNA
生物化学
基因
作者
Jinghua Chen,Rui‐Hua Xu,Junxian Xia,Jiacheng Huang,Binbin Su,Senming Wang
标识
DOI:10.1016/j.prp.2019.03.008
摘要
Epidemiological studies have illustrated that regular aspirin consumption may decrease the risk of non-small cell lung cancer (NSCLC). The present study aims to investigate the mechanism of aspirin-induced inhibition of NSCLC development during hypoxia. A549 cells were pre-treated with the vehicle control or aspirin and then subjected to hypoxic culture. Cell viability was monitored by CCK-8 assay, and flow cytometry was performed to detect cell cycle distributions, apoptosis, and proportion of cancer stem cells (CSCs). Flow cytometric cell sorting was used to separate CSCs. Quantitative reverse transcription–polymerase chain reaction and Western blot were used to detect the mRNA and protein levels of stem cell markers and the related signaling molecules. The abundance of prostaglandin E2 was detected by enzyme-linked immunosorbent assay. Exosomes in the cell culture medium were isolated using ExoQuick, and the number of exosomes was quantified by the EXOCET exosome quantification assay kit. Cell migration and angiogenesis were monitored by transwell migration assay and in vitro angiogenesis experiments. Aspirin inhibited cell proliferation and induced G2/M cell cycle arrest in hypoxic A549 cells; it also inhibited hypoxia-enhanced stemness in both A549 and ALDH+ cells. The drug reduced hypoxia-enhanced numbers of exosomes in A549 cells and exerted negative effects on the hypoxia-mediated up-regulation of exosomal HIF-1α/COX-2 and expression of exosomal miR-135b and miR-210. While hypoxic-induced exosomes can promote the proliferation, migration, and angiogenesis of other A549 cells, aspirin can weaken this promotion by reducing the amount of exosome secreted and changing exosome contents. Aspirin inhibits the hypoxia-induced stemness, hypoxic-mediated exosome release, and malignant paracrine effects of A549 cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI