CAJ | 학술논문

目的研究国家一类新药盐酸埃克替尼（ Icotinib ）对人非小细胞肺癌细胞HCC827的增殖抑制及细胞周期的影响，并探讨其作用机制。方法实验分为空白组、对照组和Icotinib处理组，采用四甲基偶氮唑盐法（ MTT）检测Icotinib 对人肺癌HCC827细胞增殖的影响；流式细胞仪检测细胞周期变化；Western blot检测相关蛋白表达，应用SPSS 13.0进行统计学分析。结果 Icotinib 以时间-剂量依赖的方式抑制HCC827细胞增殖，48 h的IC50为0.60μmol/L，72 h的IC50为0.06μmol/L；Icotinib诱导HCC827细胞发生明显的G1期阻滞并具有剂量依赖性。进一步对周期相关蛋白检测发现，Icotinib处理组较对照组相比，显著上调p21蛋白表达，抑制cyclin D1及cyclin A表达，但对cyclin E作用不明显。检测还发现Icotinib处理组明显下调ERK的磷酸化水平。结论 Icotinib能够明显抑制HCC827细胞增殖，引起细胞G1期阻滞，其机制可能与上调p21及抑制cyclin D1、cyclin A蛋白表达水平相关。并且MAPK/ERK信号通路在其介导的生物学效应中起重要作用。
목적연구국가일류신약염산애극체니（ Icotinib ）대인비소세포폐암세포HCC827적증식억제급세포주기적영향，병탐토기작용궤제。방법실험분위공백조、대조조화Icotinib처리조，채용사갑기우담서염법（ MTT）검측Icotinib 대인폐암HCC827세포증식적영향；류식세포의검측세포주기변화；Western blot검측상관단백표체，응용SPSS 13.0진행통계학분석。결과 Icotinib 이시간-제량의뢰적방식억제HCC827세포증식，48 h적IC50위0.60μmol/L，72 h적IC50위0.06μmol/L；Icotinib유도HCC827세포발생명현적G1기조체병구유제량의뢰성。진일보대주기상관단백검측발현，Icotinib처리조교대조조상비，현저상조p21단백표체，억제cyclin D1급cyclin A표체，단대cyclin E작용불명현。검측환발현Icotinib처리조명현하조ERK적린산화수평。결론 Icotinib능구명현억제HCC827세포증식，인기세포G1기조체，기궤제가능여상조p21급억제cyclin D1、cyclin A단백표체수평상관。병차MAPK/ERK신호통로재기개도적생물학효응중기중요작용。
Objective To explore the effects of icotinib on the cell proliferation and cell cycle in human non-small cell lung cancer ( NSCLC ) HCC827 cells, and to further investigate the mechanism of action . Methods Cell proliferation was measured by using MTT assay.Cell cycle changes were determined by flowcytometry.The expressions of proteins were detected by Western blot .All experimental data were dealt with SPSS(13.0 soft).Results Icotinib significantly inhibited HCC827 cell viability in a concentration and time dependentmanner,the concentration of inhibited cell viability (IC50)for 48 h was 0.60 μol/L,72 h was 0.06 μol/L.Icotinib induced significant G1 phase arrest of HCC827 cells in a concentration-dependent manner.Further more,icotinib could upregulated the expression of p21,decreased the expression of cyclin D1 and cyclin A,but had noeffect on cyclin E.In addition,after treated 24 h,icotinib could inhibit the expressions of the phosphorylated ERKobviously in HCC827 cells.Conclusions Icotinib inhibited the activation of the ERK signaling pathway ,whichconsequently upregulated the expression of p21, downregulated cyclin D1 and cyclin A in HCC827 cells.Furthermore,MAPK/ERK pathway plays an important role in the biological effects of icotinib .