Dehydroheliobuphthalmin与Lapatinib联合应用靶向抑制NCI-H441细胞的研究

Study on Targeted Inhibition of NCI-H441 Cells by Dehydroheliobuphthalmin Combined with Lapatinib

【目的】在细胞水平上探讨Dehydroheliobuphthalmin(Dehy)与Lapatinib(Lap)联合应用(Dehy+Lap)的潜在抗肿瘤机制。【方法】利用MTT,Western Blotting等方法以EGFR(wild-type)细胞NCI-H441和EGFR(mutant)细胞NCI-H1975为研究对象,对比不同处理对细胞的不同效果。【结果】在NCI-H441细胞中,Dehy+Lap联合应用降低细胞的存活率;抑制克隆形成;下调EGFR信号通路中p-EGFR、p-JNK、p-JAK、p-Stat3、p-PI3K、p-AKT蛋白表达水平;增加细胞的总凋亡率;上调细胞cleaved-Caspase-8、cleaved-Caspase-9、cleaved-Caspase-3、cleaved-PARP、Bax蛋白表达水平,下调Bcl-2蛋白表达水平;上调细胞p21、p27、p53中蛋白表达水平,下调CDK2、CDK4、CyclinD、CyclinE蛋白表达水平。在NCI-H1975细胞中Dehy+Lap联合应用未降低细胞的存活率;不抑制克隆形成;未改变相关凋亡蛋白表达水平;未改变相关周期蛋白表达水平。【结论】Dehy+Lap联合应用是一种新的抑制非小细胞肺癌细胞生长的方法,且仅对EGFR(wild-type)细胞NCI-H441有效,对EGFR(mutant)细胞NCI-H1975无效。

【Objective】The purpose of this paper is to explore the potential anti-tumor mechanism of the combined application of Dehydroheliobuphthalmin and Lapatinib at the cellular level.【Method】Using MTT,Western Blotting as the methods,EGFR(wild-type)cells NCI-H441 and EGFR(mutant)cells NCI-H1975 were used as the research objects to compare the effects of different experimental treatments on cells.【Result】In NCI-H441 cells,the treatment of Dehy+Lapt decreased cell survival rate,inhibited clone formation,down-regulated the expression of p-EGFR,p-JNK,p-JAK,p-Stat3,p-PI3 K and p-AKT in EGFR signal pathway,increased the total apoptosis rate,upregulated the expression of cleaved-Caspase-8,cleaved-Caspase-9,cleaved-Caspase-3,cleaved-PARP and Bax,and down-regulated the expression of Bcl-2.Up-regulated the protein expression levels of p21,p27 and p53,and down-regulated the protein expression levels of CDK2,CDK4,CyclinD and CyclinE.In NCI-H1975 cells,the treatment of Dehy+Lap did not reduce the cell survival rate,did not inhibit the formation of clones,did not change the expression level of related apoptotic proteins,and did not change the expression level of related cyclins.【Conclusion】The combined application of Dehydroheliobuphthalmin and Lapatinib is a new method to inhibit the growth of non-small cell lung cancer cells,and it is only effective for EGFR(wild-type)cells NCI-H441,but not for EGFR(mutant)cells NCI-H1975.