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人肺腺癌A549细胞系中侧群细胞的鉴定及其在肺癌中的潜在作用解析

Identification of side population cells in human lung adenocarcinoma A549 cell line and elucidation of the underlying roles in lung cancer.

作者信息

Xie Tong, Mo Lingzhao, Li Li, Mao Naiquan, Li Danrong, Liu Deseng, Zuo Chuantian, Huang Dingming, Pan Qi, Yang Li, Wang Shoufeng

机构信息

Department of Thoracic Surgery, The Tumor Hospital Affiliated to Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

Department of Gynecologic Oncology, The Tumor Hospital Affiliated to Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.

出版信息

Oncol Lett. 2018 Apr;15(4):4900-4906. doi: 10.3892/ol.2018.7956. Epub 2018 Feb 5.

Abstract

The present study aimed to isolate and characterize side population (SP) cells in the human lung cancer A549 cell line, and elucidate the molecular mechanism of SP cells underlying lung cancer. The SP and non-SP (NSP) cells in A549 cells were isolated and their differentiation was analyzed by fluorescence-activated cell sorting. An plate clone assay, Matrigel Transwell assay and chemoresistance analysis of the sorted SP and NSP cells were performed. In addition, the sorted SP and NSP cells were injected into BALB/c nude mice to detect their tumorigenic potential . The expression of ATP-binding cassette sub-family G member 2 (ABCG2) in transplanted tumors was detected by immunohistochemistry. The SP and NSP cells were successfully isolated. The results demonstrated that SP cells accounted for 1.09% of live A549 cells. SP cells produced SP and NSP cells, while NSP cells only produced NSP cells. In addition, SP cells formed more colonies, exhibited improved invasive ability and increased levels of chemoresistance compared with NSP cells . SP cells demonstrated a higher tumorigenic potential in BALB/c nude mice, and the number of ABCG2-positive cells in the SP xenograft tumors were significantly increased compared with that in the NSP xenograft tumors. The present study indicated that SP cells isolated from the human lung cancer A549 cell line demonstrated increased tumorigenicity, and improved invasive ability and chemoresistance compared with NSP cells. In addition, detection of ABCG2 expression may assist in predicting the chemotherapeutic outcome of patients, and serve as a target for treating lung cancer.

摘要

本研究旨在分离并鉴定人肺癌A549细胞系中的侧群(SP)细胞,并阐明SP细胞在肺癌发生中的分子机制。通过荧光激活细胞分选技术分离A549细胞中的SP细胞和非SP(NSP)细胞,并分析其分化情况。对分选后的SP细胞和NSP细胞进行平板克隆实验、基质胶Transwell实验及化疗耐药性分析。此外,将分选后的SP细胞和NSP细胞注射到BALB/c裸鼠体内,检测其致瘤潜能。通过免疫组化检测移植瘤中ATP结合盒亚家族G成员2(ABCG2)的表达。成功分离出SP细胞和NSP细胞。结果表明,SP细胞占活A549细胞的1.09%。SP细胞可产生SP细胞和NSP细胞,而NSP细胞仅产生NSP细胞。此外,与NSP细胞相比,SP细胞形成更多克隆,侵袭能力增强,化疗耐药性水平升高。SP细胞在BALB/c裸鼠中表现出更高的致瘤潜能,且SP细胞异种移植瘤中ABCG2阳性细胞数量较NSP细胞异种移植瘤显著增加。本研究表明,从人肺癌A549细胞系中分离出的SP细胞与NSP细胞相比,具有更高的致瘤性、更强的侵袭能力和化疗耐药性。此外,检测ABCG2表达可能有助于预测患者的化疗结果,并可作为治疗肺癌的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65a1/5840558/16bf303c554f/ol-15-04-4900-g00.jpg

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