加味二陈汤诱导肺癌A549移植瘤细胞凋亡的实验研究

Experimental Study on Apoptosis of Lung Cancer A549 Transplanted Tumor Cells Induced by Supplemented Decoction of Two Old Ingredients

目的:研究加味二陈汤对肺腺癌A549移植瘤生长抑制作用并初步探讨其对内质网应激反应的作用机制。方法:18只BALB/C裸鼠接种A549肺癌细胞后,随机分为对照组、加味二陈汤高剂量组(简称中药高剂量组)、加味二陈汤低剂量组(简称中药低剂量组),每组6只,分别灌胃给予生理盐水,26、13g/(kg·d)加味二陈汤水煎液,连续给药21 d。观测并分析各组肿瘤体积、瘤体生长曲线、瘤重、抑瘤率、凋亡率,并分析ATF4、CHOP蛋白表达水平。结果:与对照组比较,中药低剂量组和高剂量组裸鼠在肿瘤生长减慢、肿瘤体积缩小、瘤重降低,差异有统计学意义(P<0.05);中药低剂量组和高剂量组抑瘤率分别为21.4%、37%,与对照组比较均有统计学意义(P<0.05);对照组、中药低剂量组、中药高剂量组瘤体凋亡率分别为0.23%、0.29%、0.35%,中药高剂量组与对照组差异具有统计学意义(P<0.05);中药高剂量组和低剂量组ATF4、CHOP蛋白表达水平均较对照组上调,差异均具有统计学意义(P<0.05)。结论:加味二陈汤能诱导肺腺癌A549细胞凋亡,其机制与调控内质网蛋白ATF4、CHOP的表达水平有关。

Objective:To investigate the inhibitory effect of Supplemented Decoction of Two Old Ingredients(SDTOI)on the growth of transplanted tumor of adenocarcinoma of the lung A549 and explore its mechanism.After inoculated A549 lung cancer cells,18 BALB/C nude mice were randomly divided into a control group,a high-dose group of SDTOI,and a low-dose group of SDTOI,with 6 mice in each group.Normal saline,high and low doses of SDTOI were given to the mice by gavage.Several indices were observed and analyzed,which are the tumor volume,growth curve,weight,tumor inhibition rate and apoptosis rate.Furthermore,ATF4 and CHOP protein expression levels were also analyzed.Results:Compared with the control group,tumor growth slowed down,tumor volume decreased and tumor weight decreased in nude mice of high-dose group of SDTOI,and a low-dose group of SDTOI,and the differences are significant(P<0.05).Tumor inhibition rate was 21.4%in low-dose group of SDTOI and 37%in high-dose group of SDTOI,with a significant difference compared to the control group(P<0.05).The apoptosis rates of tumor body in the control group,low-dose group of SDTOI and high-dose group of SDTOI were 0.23%,0.29%and 0.35%,and the apoptosis rate difference between the high dose group of SDTOI and the control group was significant(P<0.05).The levels of ATF4 and CHOP protein expression in the two SDTOI groups were upregulated compared with those of the control group,and the differences were all significant(P<0.05).Conclusion:Supplemented decoction of two old ingredients can induce apoptosis of adenocarcinoma of the lung A549 cells,and this may be related to the regulation of the expression level of endoplasmic reticulum protein ATF4 and CHOP.