Lupalbigenin抑制Ba/F3 EGFR WT野生型肺癌细胞增殖作用机制

Mechanism of Inhibitory the Proliferation Effect of Lupalbigenin on Ba/F3 EGFR WT Lung Cancer Cells

在细胞水平上探讨Lupalbigenin(LG)抑制Ba/F3 EGFR WT肺癌细胞增殖的机制。使用电转染构建细胞系,利用MTS、Western blot、流式细胞术等方法构建稳定表达的EGFR(野生型)细胞Ba/F3 EGFR WT为材料,检测不同浓度化合物对细胞相关检测指标的影响。结果表明:以Ba/F3为模式细胞构建稳定表达EGFR的Ba/F3 EGFR WT肺癌细胞;在Ba/F3 EGFR WT细胞中,LG能够抑制Ba/F3 EGFR WT细胞增殖;下调EGFR信号通路中P-EGFR、P-Erk、P-Gsk-3β和P-S6蛋白水平;增加细胞总凋亡率;上调细胞中Cleaved-Caspase-3、Cleaved-Caspase-6、Cleaved-Caspase-7、Bax、Cytochrome-C蛋白水平,下调Bcl-2蛋白水平;上调细胞中P27蛋白水平,下调CDK6、Cyclin A2、Cyclin D1蛋白水平。LG是一种天然小分子化合物,能够有效抑制野生型非小细胞肺癌细胞Ba/F3 EGFR WT增殖。有望为野生型EGFR肺癌提供药物开发的新思路,并为天然化合物在治疗人类疾病中提供理论基础。

The purpose of this paper was to explore the mechanism of Lupalbigenin(LG)inhibiting the proliferation of Ba/F3 EGFR WT lung cancer cells at the cellular level.Cell line was constructed by electroporation.Stable expression of EGFR(wild type)cells Ba/F3 EGFR WT was constructed by MTS,Western blot,flow cytometry and other methods as the research object,detected the effects of cell-related detection indicators with different concentrations compound.Construction of Ba/F3 EGFR WT lung cancer cells,that stably expressing EGFR,using Ba/F3 cells as model cells.In Ba/F3 EGFR WT cell,the treatment of LG inhibited the proliferation of Ba/F3 EGFR WT cells,down-regulated the expression of P-EGFR,P-Erk,P-Gsk-3βand P-S6 in EGFR signal pathway,increased the total apoptosis rate,upregulated the expression levels of Cleaved-Caspase-3,Cleaved-Caspase-6,Cleaved-Caspase-7,Bax,and Cytochrome-C,and down-regulated the expression of Bcl-2.Up-regulated the protein expression levels of p27,and down-regulated the protein expression levels of CDK6,Cyclin A2 and Cyclin D1.LG was a natural small molecule compound that could effectively inhibit the proliferation of wild-type non-small cell lung cancer cells Ba/F3 EGFR WT.It was expected to provide new ideas for drug development for wild-type EGFR lung cancer and theoretical basis for natural compounds in the treatment of human diseases.