中国肿瘤生物治疗杂志2017，Vol.24Issue(10)：1070-1075,6.DOI:10.3872/j.issn.1007-385x.2017.10.005
瑞香狼毒提取液逆转EGFR-TKI耐药肺腺癌H1975细胞的作用及其机制
Reversal effect of extracts from stellera chamaejasme L on EGFR-TKI resistance in lung adenocarcinoma H1975 cells and its mechanism
摘要
Abstract
Objective:To investigate the reversal effects of the extracts from stellera chamaejasme L (SCL) on EG-FR-TKI (epidermal growth factor receptor tyrosine kinase inhibitors) resistance in lung adenocarcinoma H1975 cells,and to explore the underlying mechanism.Methods:The inhibitory effects of SCL,gefitinib,and SCL plus gefitinib on the proliferation of H1975 cells were evaluated by MTT assay;the effects on apoptosis of H1975 cells were determined by flow cytometry (FACS);Wound healing assay was performed to examine cell migration;and Western blotting was conducted to detect the expression of p-EGFR and apoptosis-related protein Bcl-2.Nude mice xenograft model was constructed,and the volume of xenografts as well as the overall survival (OS) was observed after treatment with SCL plus gefitinib.Moreover,ELISA was carried out to detect the serum levels of Bcl-2 and p-EGFR.Results:IC50 of SCL and gefitinib on H 1975 cells was (21.3542.11) mg/ml and (11.2141.68) μmol/L,re spectively.Compared with single treatment of SCL(5 mg/ml) or Gefitnib(1 μmol/L),combined treatment of SCL and gefitnib significantly inhibited the proliferation rate of H1975 cells ([49.78±7.09]％ vs [12.88±3.64]％,[8.45± 2.57]％;all P＜0.01),and inhibited the migration ofH1975 cells ([22.4± 6.5]％ vs [70.3 ±4.9]％,[67.1 ± 10.5]％;all P＜0.01).FACS showed that the apoptosis rate in combined treatment group was obviously higher than that in single treatment group ([51.68±6.56]％ vs [9.88±2.71]％,[9.48±2.45]％;all P＜0.01).Western blotting showed the protein expressions of Bcl-2 and p-EGFR in H1975 cells were remarkably decreased after the combined treatment of SCL and gefitinib (P＜0.01).In vivo xenograft experiment showed that combined treatment of SCL and gefitinib significantly inhibited progressive tumor growth and promoted the survival time compared with single treatment of SCL or gefitinib (all P＜0.01).Conclusion:SCL might reverse the EGFR-TKI resistance in H 1975 cells.The potential mechanism might be related to phosphorylation of EGFR and down-regulation of Bcl-2 expression,which might provide new thoughts of treating lung adenocarcinoma.关键词
瑞香狼毒/吉非替尼/表皮生长因子受体酪氨酸激酶抑制剂/H1975细胞/肺腺癌Key words
stellera chamaejasme L(SCL)/gefitinib/epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI)/H1975 cell/lung adenocarcinoma分类
医药卫生引用本文复制引用
孙伟红,刘淑娟,唐淑美,马学真,魏晓芳,朱丹妮,宋海平..瑞香狼毒提取液逆转EGFR-TKI耐药肺腺癌H1975细胞的作用及其机制[J].中国肿瘤生物治疗杂志,2017,24(10):1070-1075,6.基金项目
山东省医药卫生科技发展计划资助项目(No.2016WS0324). Project supported by Medical and Health Technology Development Program of Shandong Province(No.2016WS0324) （No.2016WS0324）
