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非小细胞肺癌中ARL4C的表达及其在EGFR-TKI耐药中的作用
引用本文:陈增,廖锦容,苏颖,何志勇,胡丹,林可焴,金善丰,林仁章,林贤东. 非小细胞肺癌中ARL4C的表达及其在EGFR-TKI耐药中的作用[J]. 肿瘤防治研究, 2020, 47(7): 498-503. DOI: 10.3971/j.issn.1000-8578.2020.19.1504
作者姓名:陈增  廖锦容  苏颖  何志勇  胡丹  林可焴  金善丰  林仁章  林贤东
作者单位:1. 350014 福州,福建省肿瘤医院,福建医科大学附属肿瘤医院放射生物学及肿瘤放射治疗研究室;2. 350014 福州,福建省肿瘤医院,福建医科大学附属肿瘤医院肿瘤内科;3. 350014 福州,福建省肿瘤医院,福建医科大学附属肿瘤医院病理科;4. 350014 福州,福建省科技厅转化医学重点实验室
基金项目:福建省卫生教育联合攻关项目(WKJ2016-2-05);;福建省自然科学基金(2019J01196);
摘    要:目的探讨非小细胞肺癌中ARL4C的表达及其与临床病理特征的关系以及在EGFR-TKI耐药中的作用。方法收集63例NSCLC患者的癌组织和癌旁组织,qRT-PCR法检测ARL4C的表达并分析其与临床病理特征之间的关系。qRT-PCR和Western blot法检测ARL4C在各细胞株中的表达,MTS检测细胞活性及IC50的变化,Transwell侵袭实验检测ARL4C表达变化对细胞侵袭能力的影响。结果非小细胞肺癌组织中ARL4C表达水平低于癌旁组织(P<0.05),其表达水平与淋巴结转移、TNM分期和肺膜侵犯密切相关(P<0.05)。TKI耐药细胞株HCC827/ER中ARL4C在mRNA以及蛋白表达水平相较对照细胞株HCC827显著下调(P<0.05);ARL4C过表达细胞株HCC827/ER/ARL4C-OE IC50显著下降(P<0.05),Transwell分析结果显示过表达ARL4C后肺癌细胞的侵袭能力受到抑制(P<0.05)。结论 ARL4C异常表达与非小细胞肺癌淋巴结转移、TNM分期和肺膜侵犯密切相关...

关 键 词:ARL4C  非小细胞肺癌  EGFR-TKI  获得性耐药
收稿时间:2019-12-10

Expression of ARL4C in Non-small Cell Lung Cancer and Its Role in EGFR-TKI Resistance
CHEN Zeng,LIAO Jinrong,SU Ying,HE Zhiyong,HU Dan,LIN Keyu,JIN Shanfeng,LIN Renzhang,LIN Xiandong. Expression of ARL4C in Non-small Cell Lung Cancer and Its Role in EGFR-TKI Resistance[J]. Cancer Research on Prevention and Treatment, 2020, 47(7): 498-503. DOI: 10.3971/j.issn.1000-8578.2020.19.1504
Authors:CHEN Zeng  LIAO Jinrong  SU Ying  HE Zhiyong  HU Dan  LIN Keyu  JIN Shanfeng  LIN Renzhang  LIN Xiandong
Affiliation:1. Laboratory of Radiation Oncology and Radiobiology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350014, China; 2. Department of Oncology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350014, China; 3. Department of Pathology, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350014, China; 4. Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China
Abstract:Objective To investigate the expression of ARL4C in NSCLC and its correlation with clinicopathological features, as well as its role in EGFR-TKI resistance. Methods We collected the tumor and adjacent tissues of 63 NSCLC patients. The mRNA expression of ARL4C was detected by qRTPCR and the relation between ARL4C and clinicopathological features was analyzed. The expressions of ARL4C in TKI-resistant cell line, control cell line and ARL4C overexpressing cell line were assessed by qRT-PCR and Western blot. The changes of cell activity and IC50 were detected by MTS. Transwell invasion assay was used to detect the effect of ARL4C expression on cell invasion. Results The expression level of ARL4C in NSCLC tissues was lower than that in adjacent tissues (P<0.05). The expression of ARL4C in NSCLC was closely related to lymph node metastasis, TNM stage and pulmonary membrane invasion (P<0.05). Compared with control cell line HCC827, the expression levels of ARL4C mRNA and protein in TKI-resistant cell line HCC827/ER and the IC50 of ARL4C overexpressing TKI-resistant cell line HCC827/ER/ARL4C-OE were significantly lower (P<0.05). Transwell assay results showed that the overexpression of ARL4C inhibited the invasion of lung cancer cell line (P<0.05). Conclusion The abnormal expression of ARL4C is closely related to lymph node metastasis, TNM stage and pulmonary membrane invasion of NSCLC. Overexpression of ARL4C may improve the sensitivity of NSCLC cells to EGFR-TKI and inhibit the invasion of NSCLC cells.
Keywords:ARL4C  Non-small cell lung cancer  EGFR-TKI  Acquired drug resistance  
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