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碱性成纤维细胞生长因子信号调节肺癌 A549 细胞中的癌症干细胞。

Basic fibroblast growth factor signalling regulates cancer stem cells in lung cancer A549 cells.

机构信息

Department of Oncology, Chengdu Fifth People's Hospital, Chengdu, China.

Pulmonary and Critica Care Medicine, Chengdu Fifth People's Hospital, Chengdu, China.

出版信息

J Pharm Pharmacol. 2019 Sep;71(9):1412-1420. doi: 10.1111/jphp.13136. Epub 2019 Jul 8.

DOI:10.1111/jphp.13136
PMID:31282010
Abstract

OBJECTIVES

The basic fibroblast growth factor (bFGF)/fibroblast growth factor receptor (FGFR) signal transductional pathway plays an important role not only in tumour, but also in tumour stem cells. Thus, this study was designed to investigate the effects of bFGF signalling on cancer stem cells of lung cancer.

METHODS

We blocked bFGF/FGFR signalling in cisplatin (DDP) selected A549 by knocking down bFGF via RNA interference, and subsequently, the stem cell marker of OCT-4 was determined, and cell proliferation, clone formation, invasiveness, apoptosis and drug resistance abilities of DDP selected A549 cells were investigated.

KEY FINDINGS

The expressions of bFGF and OCT-4 in DDP selected A549 were higher than that of A549 cells. The findings suggested blocking of bFGF/FGFR signalling resulted in downregulation of bFGF, reduction in cell proliferation, clone formation, invasion and drug resistance abilities, and increase in cell apoptosis. Furthermore, our results also revealed OCT-4 was reduced after bFGF signalling blocking.

CONCLUSIONS

In conclusion, our study suggested that bFGF/FGFR signalling plays an important role in maintaining lung cancer stem cell characteristics and regulating expression of cancer stem cell marker of OCT-4.

摘要

目的

碱性成纤维细胞生长因子(bFGF)/成纤维细胞生长因子受体(FGFR)信号转导通路不仅在肿瘤中,而且在肿瘤干细胞中都起着重要作用。因此,本研究旨在探讨 bFGF 信号对肺癌肿瘤干细胞的影响。

方法

我们通过 RNA 干扰敲低 bFGF,阻断顺铂(DDP)选择的 A549 中的 bFGF/FGFR 信号,随后确定 OCT-4 干细胞标志物,并研究 DDP 选择的 A549 细胞的增殖、克隆形成、侵袭、凋亡和耐药能力。

主要发现

DDP 选择的 A549 中的 bFGF 和 OCT-4 的表达高于 A549 细胞。结果表明,阻断 bFGF/FGFR 信号导致 bFGF 下调,细胞增殖、克隆形成、侵袭和耐药能力降低,细胞凋亡增加。此外,我们的结果还表明,阻断 bFGF 信号后 OCT-4 减少。

结论

总之,我们的研究表明,bFGF/FGFR 信号在维持肺癌干细胞特征和调节 OCT-4 肿瘤干细胞标志物的表达中起着重要作用。

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