文章摘要
袁 渊,束永前.联合应用三苯氧胺和吉非替尼对NSCLC细胞的抗增殖效应[J].南京医科大学学报,2008,28(4):467~471
联合应用三苯氧胺和吉非替尼对NSCLC细胞的抗增殖效应
Antiproliferative effects on non-small cell lung cancer cells by combining Tamoxifen and Gefitinib
投稿时间:2007-12-14  
DOI:10.7655
中文关键词: 三苯氧胺  吉非替尼  NSCLC  EGFR  ERβ
英文关键词: Tamoxifen  Gefitinib  NSCLC  EGFR  ERβ
基金项目:
作者单位
袁 渊 南京医科大学第一附属医院肿瘤生物治疗中心江苏 南京 210029 
束永前  
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中文摘要:
      目的:探讨雌激素受体拮抗剂三苯氧胺联合表皮生长因子受体抑制剂吉非替尼对人小细胞肺癌(NSCLC)细胞株增殖和凋亡的影响及相关的分子机制,为联合分子靶向和激素治疗NSCLC提供理论依据。方法:以吉非替尼及三苯氧胺单独或联合处理NSCLC细胞株,MTT法比较细胞增殖,流式细胞仪检测细胞凋亡。应用荧光定量PCR及Western blot检测三种肺癌细胞株中表皮生长因子受体(EGFR)及雌激素受体β(ERβ)的表达情况,并分别检测雌二醇,三苯氧胺(TAM)对细胞中EGFR,以及表皮生长因子(EGF)和吉非替尼对ERβ表达的影响,同时还检测了雌二醇对EGFR的磷酸化作用。结果:联合吉非替尼和三苯氧胺增强对EGFR,ERβ阳性的A549,H1650细胞的抑制作用,促进凋亡,但对EGFR,ERβ阴性的H520细胞无明显改变。雌二醇可促进细胞EGFR磷酸化,却也抑制其表达,而三苯氧胺则上调EGFR的表达。同时,EGF及吉非替尼对ERβ的表达也有类似的相反的调控作用。结论:联合吉非替尼和三苯氧胺能够增强对EGFR,ERβ均阳性的肺癌细胞的抗增殖作用,这可能与细胞内EGFR信号转导途径和雌激素信号通路的交叉有关。因此,结合针对EGFR的分子靶向治疗与激素治疗可能为肺癌的治疗提供新的途径。
英文摘要:
      Objective:To identify the effect of oestrogen receptor(ER) antagonist,Tamoxifen,combination with EGFR tyrosine kinase inhibitor,Gefitinib,on the proliferation and apoptosis in non-small cell lung cancer(NSCLC) cell lines and the related molecular mechanism,providing theoretical evidence for the molecular targeted treatment combination with endocrine treatment in NSCLC. Methods:The cell lines were treated with gefitinib and tamoxifen alone or in combination. The cell proliferation were detected with MTT,the cell apoptosis with flow cytometry and the expression of EGFR and ERβ with real-time PCR and Western blot. In addition,the effect of oestrogen and Tamoxifen on the expression of EGFR,the effect of EGF and Gefitinib on the expression of ERβ were detected,respectively. The effect of oestrogen on the phospho-EGFR were also detected. Results:The combination of Tamoxifen and Gefitinib increased the inhibition and apoptosis in EGFR and ERβ positive cell lines A549 and H1650,while showed no significant changes in EGFR and ER negative cell line H520. It was found that oestrogen could promote the phospho-EGFR protein expression,meanwhile,EGFR protein expression was down-regulated in response to estrogen and up-regulated in response to Tamoxifen in vitro. Conversely,ERβ expression was decreased in response to EGF and increased in response to Gefitinib. Conclusion:The combination of Tamoxifen and Gefitinib can promote its antiproliferative effects on EGFR and ERβ positive lung cell lines. These results suggested that this might be involved in cross-signaling between the EGFR/ER pathways in NSCLC. In conclusion,it provided the rationale to combine Gefitinib with hormone therapy for lung cancer treatment.
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