非小细胞肺癌中ARL4C的表达及其在EGFR-TKI耐药中的作用

陈增; 廖锦容; 苏颖; 何志勇; 胡丹; 林可焴; 金善丰; 林仁章; 林贤东

doi:10.3971/j.issn.1000-8578.2020.19.1504

非小细胞肺癌中ARL4C的表达及其在EGFR-TKI耐药中的作用

Expression of ARL4C in Non-small Cell Lung Cancer and Its Role in EGFR-TKI Resistance

摘要

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。过表达ARL4C能提高非小细胞肺癌细胞对EGFR-TKI药物的敏感度并抑制非小细胞肺癌细胞的侵袭能力。

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 qRT-PCR 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.

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