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基于Caspase-3/Caspase-8通路探讨复方藤梨汤对HCT116结肠癌细胞裸鼠移植瘤生长的影响
古 佳,刘 强,史梦娇
0
(贵州中医药大学,贵州 贵阳,550005;贵州中医药大学第一附属医院,贵州 贵阳,550001)
摘要:
目的:研究复方藤梨汤对人结肠癌HCT116细胞裸鼠移植瘤生长的影响,并探讨其对肿瘤组织凋亡及相关基因表达的影响。方法:建立人结肠癌HCT116细胞移植瘤裸鼠模型,将其随机分为模型组和复方藤梨汤药物组(低、中、高剂量组),分别给予不同剂量复方藤梨汤(12、24、48 g/kg)及等体积0.9%氯化钠注射液进行灌胃。取裸鼠移植瘤,检测质量并计算不同剂量复方藤梨汤的抑瘤率;采用TUNEL检测肿瘤组织细胞凋亡情况;苏木精-伊红(HE)检测肿瘤组织细胞密度及转移情况;蛋白质印迹法(WB)检测移植瘤半胱氨酸蛋白酶-3(Caspase-3)、半胱氨酸蛋白酶-8(Caspase-8)蛋白表达情况。结果:与模型组相比,瘤体质量随着药物剂量增加而减小,其中复方藤梨汤高剂量组瘤重低于模型组(P<0.05),抑瘤率随剂量增加而增加,肿瘤组织细胞凋亡程度随剂量增加而增加。 随着复方藤梨汤剂量的升高,药物组瘤块组织细胞排列稀疏,密度减小,细胞形态不完整或消失,细胞间隙增大,出现坏死区域。与模型组相比,复方藤梨汤低、中、高剂量组Caspase-3和Caspase-8的蛋白表达量均升高,存在一定剂量依赖性(P<0.05)。结论:复方藤梨汤抑制人结肠癌HCT116细胞裸鼠移植瘤生长,机制可能与其激活Caspase-3、Caspase-8的蛋白表达、诱导细胞凋亡有关。
关键词:  人结肠癌HCT116细胞  复方藤梨汤  移植瘤  细胞凋亡  半胱氨酸蛋白酶-3  半胱氨酸蛋白酶-8
DOI:
Effect of compound Tengli decoction on the growth of nude mouse xenograft tumor established by human colon cancer HCT116 cells:A study based on the Caspase-3/Caspase-8 pathway
GU Jia,LIU Qiang,SHI Mengjiao
(Guizhou University of Traditional Chinese Medicine,Guiyang 550005,Guizhou,China;The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550000,Guizhou,China)
Abstract:
Objective:To investigate the effect of compound Tengli decoction on the growth of nude mouse xenograft tumor established by human colon cancer HCT116 cells,as well as its effect on apoptosis and the expression of related genes in tumor tissue.Methods:A nude mouse xenograft tumor model of human colon cancer HCT116 cells was established,and then the nude mice were randomly divided into model group (treated with an equal volume of 0.9% sodium chloride injection by gavage) and low-,middle-,and high-dose compound Tengli decoction groups (treated with compound Tengli decoction at a dose of 12,24,and 48 g/kg,respectively).The nude mouse xenograft tumor was collected and weighed,and the tumor inhibition rate of compound Tengli decoction at different doses was calculated.The TUNEL method was used to measure cell apoptosis in tumor tissue;HE staining was used to measure cell density of metastasis in tumor tissue;Western blot was used to measure the protein expression levels of Caspase-3 and Caspase-8 in xenograft tumor.Results:Compared with the model group,the weight of tumor decreased with the increase in dose,and the high-dose compound Tengli decoction group had a significantly lower tumor weight than the model group (P<0.05);tumor inhibition rate increased with the increasing dose,and the degree of cell apoptosis in tumor tissue also increased with the increase in dose.As the dosage of the compound Tengli decoction increased,the tumor tissue exhibited progressively disorganized cell arrangement and reduced cell density.Cell morphology became incomplete or disappeared,intercellular spaces widened,and necrotic areas emerged.Compared with the model group,the low-,middle-,and high-dose compound Tengli decoction groups had significant increases in the protein expression levels of Caspase-3 and Caspase-8 in a dose-dependent manner to a certain extent (P<0.05).Conclusion:Compound Tengli decoction can inhibit the growth of nude mouse xenograft tumor of human colon cancer HCT116 cells,possibly by activating the protein expression of Caspase-3 and Caspase-8 and inducing cell apoptosis.
Key words:  human colon cancer HCT116 cells  compound Tengli decoction  xenograft tumor  cell apoptosis  Caspase-3  Caspase-8

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