Suberoylanilide hydroxamic acid overcomes erlotinib-acquired resistance via phosphatase and tensin homolog deleted on chromosome 10-mediated apoptosis in non-small cell lung cancer  

作　　者：Peng-Fei Wu Wei-Wei Gao Cui-Lan Sun Tai Ma Ji-Qing Hao 

机构地区：[1]Department of Oncology,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China

出　　处：《Chinese Medical Journal》2020年第11期1304-1311,共8页中华医学杂志（英文版）

摘　　要：Background::Epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs),such as erlotinib and gefitinib,are widely used to treat non-small cell lung cancer(NSCLC).However,acquired resistance is unavoidable,impairing the anti-tumor effects of EGFR-TKIs.It is reported that histone deacetylase(HDAC)inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy.However,whether the HDAC inhibitor suberoylanilide hydroxamic acid(SAHA)can overcome erlotinib-acquired resistance is not fully clear.Methods::An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures.NSCLC cells were co-cultured with SAHA,erlotinib,or their combination,and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting.Finally,the expression of phosphatase and tensin homolog deleted on chromosome 10(PTEN)was assessed by western blotting.Results::The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line.PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells,and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells.Furthermore,treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.Conclusions::PTEN deletion is closely related to acquired resistance to EGFR-TKIs,and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy.SAHA enhances the suppressive effects of erlotinib in lung cancer cells,increasing cellular apoptosis and PTEN expression.SAHA can be a potential adjuvant to erlotinib treatment,and thus,can improve the effica

关 键 词：Acquired resistance ERLOTINIB Histone deacetylase Lung cancer SAHA 

分 类 号：R734.2[医药卫生—肿瘤]