灵芝乙醇提取物对肺癌细胞增殖抑制的作用及分子机制

Inhibitory effects of Ganoderma lucidum ethanol extracts on proliferation of lung cancer cells and its molecular mechanism

目的探讨灵芝乙醇提取物(GLEE)对非小细胞肺癌A549细胞增殖抑制的作用及分子机制。方法建立A549肺癌荷瘤鼠模型,每日ig给予荷瘤鼠50、100、150 mg·kg^(-1)的GLEE,计算抑瘤率、肿瘤体积及脏器系数;用Western blot法分析GLEE对A549细胞中相关蛋白表达的影响;用RNA-seq分析GLEE对A549细胞中基因表达的影响。结果实验的第16~20天,50、100、150 mg·kg^(-1) GLEE显著抑制肿瘤生长,抑瘤率分别为24.52%、40.69%、51.35%;在蛋白水平,GLEE通过下调Bcl-2,上调Bax和激活Caspase-3诱导细胞凋亡;火山图显示:A549细胞中4572个基因上调,4464个基因下调。结论GLEE对非小细胞肺癌A549细胞增殖具有显著抑制作用,其诱导细胞的凋亡可能是通过线粒体途径。

OBJECTIVE To investigate the inhibitory effects of Ganoderma lucidum ethanol extracts(GLEE)on the proliferation of non-small cell lung cancer A549 cells and its molecular mechanism.METHODS A nude mouse model bearing A549 lung cancer cells was established.Tumor-bearing mice were given 50,100 and 150 mg·kg^(-1) GLEE daily by intragastric gavage,and the tumor inhibition rate,tumor volume and organ index were calculated.Western blot was used to analyze the effect of GLEE on the expression of related proteins in A549 cells.RNA-seq was used to analyze the effect of GLEE on the gene expression of A549 cells.RESULTS From the 16th to the 20th day of the experiment,low,medium and high doses of GLEE(50,100,150 mg·kg^(-1))significantly inhibited tumor growth.The tumor inhibition rates of the low,medium and high dose groups were 24.52%,40.69%and 51.35%,respectively.GLEE induced apoptosis at the protein level by down-regulating Bcl-2,up-regulating Bax and activating Caspase-3.The volcano map showed that 4572 genes were up-regulated and 4464 genes were down-regulated in A549 cells.CONCLUSION GLEE has a significant inhibitory effect on the proliferation of non-small cell lung cancer A549 cells.GLEE might induce cell apoptosis through the mitochondrial pathway.