蠲瘤散结方抑制肺腺癌A549细胞移植瘤的增殖及可能作用机制的探讨

Juan Liu San Jie Formula inhibits the proliferation of lung adenocarcinoma A549 cells xenograft and its possible mechanism

目的:探讨中药蠲瘤散结方对荷人肺腺癌小鼠皮下移植瘤生长的影响及可能的作用机制。方法:体外培养人肺腺癌A549细胞,采用皮下接种的方法构建裸小鼠A549细胞移植瘤模型。实验分3组:对照组(0.9%的氯化钠溶液)、顺铂(阳性对照组)和蠲瘤散结方组,通过比较移植瘤体积和质量等指标观察蠲瘤散结方对肿瘤生长的影响。随后,采用表达谱基因芯片技术检测对照组和蠲瘤散结方组中各3个肿瘤样本基因的表达水平,筛选差异表达的基因并进行功能分析。结果:与对照组相比,顺铂组和蠲瘤散结方组移植瘤的质量和体积均明显降低,差异有统计学意义(P值均<0.05);蠲瘤散结方组移植瘤的质量和体积略高于顺铂组,但二组间差异无统计学意义(P>0.05)。蠲瘤散结方组小鼠的体质量与对照组相比差异无统计学意义(P>0.05),蠲瘤散结方组和对照组小鼠的体质量都明显高于顺铂组(P值均<0.05)。采用表达谱基因芯片技术检测对照组和蠲瘤散结方组移植瘤中RNA的表达情况,共筛选获得261个差异表达的基因,其中85个基因表达上调,176个基因表达下调。对差异表达基因的分析显示,蠲瘤散结方调控的差异基因多与代谢相关,如卵巢类固醇生成通路、糖脂代谢通路和视黄醇代谢通路等。结论:蠲瘤散结方能够明显抑制小鼠体内肺腺癌的生长,这一作用可能与其调节肿瘤细胞的异常代谢有关。

Objective:To investigate the effect of Chinese medicine Juan Liu San Jie Formula on subcutaneous xenograft in mice bearing human lung adenocarcinoma,and to explore its possible molecular mechanism.Methods:The human lung adenocarcinoma A549 cells were cultured in vitro,and the xenograft tumor models of BALB/c-nu/nu mice were constructed by subcutaneous inoculation.The experiment was divided into three groups:control group(0.9%sodium chloride solution),cisplatin treatment group(positive control)and Juan Liu San Jie Formula treatment group.The effect of Juan Liu San Jie Formula on tumor growth by comparing tumor volume and weight.After the experiment,Gene Chip technology was used to detect differential expression genes between control group and Juan Liu San Jie Formula treatment group,to screen the differentially expressed genes and analyze their functions.Results:Comparing with the control group,the xenograft tumor weight and volume in the mice treated with Juan Liu San Jie Formula and cisplatin were significantly reduced(both P<0.05).Moreover,the tumor weight and volume of mice in Juan Liu San Jie Formula treatment group was slightly larger than those in the cisplatin treatment group(both P>0.05).There was no significant difference in the weight of the mice between the Juan Liu San Jie Formula treatment group and the control group(P>0.05),but the weight of the Juan Liu San Jie Formula treatment group and the control group was significantly higher than the cisplatin treatment group(both P>0.05).Gene chip results showed that compared with the control group,the Juan Liu San Jie Formula treatment group had screened 261 differentially expressed genes,of which 85 genes were up-regulated and 176 genes were down-regulated.Differential gene analysis showed that gene expression regulated by Juan Liu San Jie Formula was mostly related to metabolism,such as ovarian steroid production pathway,glycolipid metabolism pathway and retinol metabolism pathway.Conclusion:Juan Liu San Jie Formula can inhibit the growth of human lung adenocarcinoma in mice,which may be related to its regulation of abnormal metabolism of tumor cells.