中国肺癌杂志2018，Vol.21Issue(2)：89-98,10.DOI:10.3779/j.issn.1009-3419.2018.02.03
囊性纤维化跨膜转导调节子(CFTR)对肺癌A549细胞恶性特性的影响研究
Impact of Cystic Fibrosis Transmembrane Conductance Regulator on Malignant Properties of KRAS Mutant Lung Adenocarcinoma A549 Cells
摘要
Abstract
Background and objective The incidence of lung cancer is gradually increased, and the cystic fi-brosis transmembrane conductance regulator (CFTR) has recently demonstrated to have an implication in the deonco-genesis and malignant transformation of many types of cancers. The aim of this study is to investigate impacts of CFTR on the malignant features of lung adenocarcinoma A549 cells. Methods The capacity of cell proliferation, migration, invasion and clonogenicity of non-small cell lung cancer A549 cells were detected by CCK8 cell proliferation assay, cell scratch assay,Transwell cell invasion assay and clone formation assay,respectively.Meanwhile,the effect of CFTR gene on the expression of cancer stem cell related transcriptional factors was also detected by immunoblotting (West-ern blot)assay.Results An overexpression of CFTR gene in A549 cells significantly inhibited the malignant capacity of A549 cells, including potencies of cell proliferation, migration, invasion and colony formation; while knockdown of CFTR gene expression by RNA interference in A549 cells resulted in an opposite effect seen in above cells overexpress-ing CFTR gene.Mechanistically,immunoblotting assay further revealed that the ectopic expression of CFTR gene led an inhibitory expression of stem cell-related transcriptional factors SOX2 and OCT3/4, and cancer stem cell surface marker CD133 in A549 cells, while a knockdown of CFTR expression yielded a moderately increased expression of these gene.However,an alteration of CFTR gene expression had neither effect on the expression of putative lung can-cer stem cell marker aldehyde dehydrogenase1 (ALDH1), nor the frequency of ALDH1A-positive cells in A549 cells, as ascertained by the immunoblotting assay and cytometry analysis, respectively. Conclusion The CFTR exhibited an inhibitory role in the malignancy of lung adenocarcinoma A549 cells, suggesting that it may be a novel potential target for lung cancer treatment. However, its functions in other lung adenocarcinoma cell lines and its underlying molecular mechanisms require further investigation.关键词
囊性纤维化跨膜转导调节子/肺腺癌/A549细胞Key words
Cystic fibrosis transmembrane conductance regulators/Lung neoplasms/A549 cells引用本文复制引用
李惠,王颖,杨佳丽,刘晓明,石娟..囊性纤维化跨膜转导调节子(CFTR)对肺癌A549细胞恶性特性的影响研究[J].中国肺癌杂志,2018,21(2):89-98,10.基金项目
本研究受国家自然科学基金项目(No.31472191)、宁夏医科大学2017年校级科研项目(No.XY2017171)、宁夏医科大学临床医学一流学科建设项目(No.YXW2017014)和2017年宁夏"研究生教育创新计划"学位点建设项目(No.YXW2017014)资助 This study was supported by the grants from the National Natural Science Foundation of China(to Xiaoming LIU)(No.31472191),2017 school-level scientific research projects of Ningxia Medical University(to Juan SHI)(No.XY2017171),First-class Discipline construction of clinical medicine of Ningxia Medical University(to Hui LI)(No.YXW2017014),and plan of Post-graduate Education innovation Discipline construction project of Ningxia,China(to Hui LI)(No.YXW2017014). （No.31472191）
