[Expression of Acetaldehyde Dehydrogenase in Gefitinib-resistant Human Lung Adenocarcinoma HCC-827/GR Cells]

Zhongguo Fei Ai Za Zhi. 2018 Jun 20;21(6):431-436. doi: 10.3779/j.issn.1009-3419.2018.06.01.
[Article in Chinese]

Abstract

Background: Tumor recurrence and drug resistance are the main causes of death in tumor patients. The family of acetaldehyde dehydrogenase (ALDH) is closely related to the proliferation, migration, invasion and resistance of tumor cells, and different ALDH subtypes are expressed in different tumor cells. The aim of this study is to elucidate the ALDH subtype in human lung adenocarcinoma HCC-827/GR cells, which resistant to the gefitinib.

Methods: The human lung adenocarcinoma HCC-827 cells were used to generate the gefitinib-resistant HCC-827/GR cells; the expression of ALDH subtype in either HCC-827 or HCC-827/GR was detected by flow cytometry; The proliferative capacity and sensitivity to gefitinib of hcc-827/GR cells were analyzed by MTT assay before and after treatment with 100 μmol/L diethyllaminaldehyde (DEAB); Real-time quantitative PCR was used to detect the expression of ALDH subtypes at mRNA levels in hcc-827 cells and hcc-827/GR cells.

Results: Compared with HCC-827 cells, the positive rate of ALDH in HCC-827/GR cells increased. The proliferation ability of HCC-827/GR cells decreased after treatment with 100 μmol/L DEAB. Compared with HCC-827 cells, the expression of ALDH1A1 and ALDH1L1 mRNA was increased in hcc-827/GR cells, but the ALDH3B2 expression was decreased.

Conclusions: ALDH might be used as a molecular biomarker to test the gefitinib-resistant to lung adenocarcinoma cancer cells, and the ALDH1A1 may play a role in gefitinib resistance in lung cancer.

【中文题目:吉非替尼耐药的人肺腺癌HCC-827/GR细胞 乙醛脱氢酶亚型表达分析】 【中文摘要:背景与目的 肿瘤的复发和耐药是肿瘤患者死亡的主要原因。乙醛脱氢酶(acetaldehyde dehydrogenase, ALDH)家族与肿瘤细胞的增殖、迁移、侵袭和耐药密切相关,且ALDH不同亚型基因在不同肿瘤细胞中有差异性表达。本实验旨在分析对吉非替尼耐药的人肺腺癌细胞HCC-827/GR ALDH亚型的表达。方法 利用人肺腺癌细胞系HCC-827制备吉非替尼耐药细胞株HCC-827/GR;利用流式检测HCC-827及HCC-827/GR中ALDH的表达;采用MTT法检测ALDH抑制剂二乙氨基苯甲醛(diethyllaminaldehyde, DEAB)处理前后HCC-827/GR细胞的增殖能力和对吉非替尼的敏感性;利用qRT-PCR检测HCC-827与HCC-827/GR细胞中ALDH各亚型在mRNA水平的表达。结果 与HCC-827细胞相比,ALDH在吉非替尼耐药的细胞株HCC-827/GR的阳性率增加;经100 μmol/L DEAB处理后,HCC-827/GR细胞增殖能力下降;与HCC-827细胞相比,ALDH1A1和ALDH1L1在HCC-827/GR细胞中mRNA表达水平增高;ALDH3B2表达降低。结论 ALDH具有检测吉非替尼耐药的人肺腺癌细胞的标志分子的潜力,其中ALDH1A1可能参与人肺腺癌细胞对吉非替尼耐药性的形成过程。】 【中文关键词:人肺腺癌;HCC-827;吉非替尼;乙醛脱氢酶】.

Keywords: Acetaldehyde dehydrogenase; Gefitinib; HCC-827; Human lung adenocarcinoma.

MeSH terms

  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Aldehyde Oxidoreductases / antagonists & inhibitors
  • Aldehyde Oxidoreductases / genetics*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics*
  • Enzyme Inhibitors / pharmacology
  • Gefitinib
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Lung Neoplasms / pathology*
  • Quinazolines / pharmacology*

Substances

  • Enzyme Inhibitors
  • Quinazolines
  • Aldehyde Oxidoreductases
  • aldehyde dehydrogenase (NAD(P)+)
  • Gefitinib

Grants and funding

本研究受宁夏医科大学科学基金资助项目(No.XQ201332)资助