姜黄素对HepG2裸鼠移植瘤的抑制作用及对瘤体组织中NLRP3、IL-1β表达的影响

Inhibitory effect of curcumin on transplanted tumor of HepG2 cells in nude mice and on the expression of NLRP3 and IL-1βin tumor tissue

目的探究姜黄素对HepG2细胞裸鼠移植瘤的抑制作用以及对瘤体组织中NLRP3、IL-1β表达的影响。方法将50只BALB/c-nu裸鼠随机分为模型组,姜黄素低、中、高剂量组及顺铂组,每组10只。采用裸鼠成瘤实验观察姜黄素对人肝癌细胞HepG2裸鼠移植瘤生长的抑制作用,TUNEL实验比较肝癌细胞凋亡情况,比较各组裸鼠肿瘤组织微血管密度,qRT-PCR法及Western blot法比较裸鼠肿瘤组织中NLRP3、IL-1βmRNA及蛋白的相对表达量。结果与模型对照组相比,不同剂量姜黄素干预后裸鼠的肿瘤质量和体积均显著减少(P<0.05),高剂量姜黄素裸鼠肿瘤质量和体积减少最为明显(P<0.05)。与模型对照组相比,姜黄素低、中、高剂量组和顺铂组裸鼠肝癌细胞凋亡指数均显著增加(P<0.05),凋亡指数排序为姜黄素高剂量组>中剂量组>低剂量组(P<0.05)。姜黄素低、中、高剂量组和顺铂组裸鼠的微血管数目较模型对照组裸鼠显著减少(P<0.05)。与模型对照组相比,不同浓度姜黄素干预后裸鼠肿瘤组织中的NLRP3、IL-1βmRNA和蛋白相对表达量均呈不同程度降低(P<0.05),且姜黄素浓度越高,裸鼠肿瘤组织中NLRP3、IL-1βmRNA和蛋白相对表达量表达降低越显著(P<0.05)。结论姜黄素抗肝细胞癌的作用机制可能与促进肝癌细胞凋亡及调控NLRP3、IL-1β表达水平相关。

Objective To determine the inhibitory effect of curcumin on HepG2 cell transplanted tumor in nude mice and its effect on the expression of NLRP3 and IL-1β.Methods Fifty BALB/c-nu nude mice were randomly divided into a model control group,3 curcumin(low,medium and high dose)groups,and a cisplatin group(10 rats in each group).The inhibitory effect of curcumin on the growth of transplanted tumor of human hepatoma cell HepG2 in nude mice was observed by nude mouse tumorigenesis experiment.The apoptosis of hepatoma cells was compared by TUNEL experiment;the microvessel density of tumor tissue in nude mice was compared;NLRP3 and IL-1βprotein and relative expression in the tumor tissue of nude mice were compared by Western blot and qRT-PCR.Results Compared with the model control group,the mass and volume of tumor in the nude mice were significantly decreased after different doses of curcumin(P<0.05).The mass and volume of tumor in the nude mice with high doses of curcumin were decreased most(P<0.05).Compared with the model control group,the apoptosis index of HCC cells in the low dose,medium dose,high dose groups and the cisplatin group was significantly increased(P<0.05),and the order of apoptosis index was high dose group>medium dose group>low dose group(P<0.05).The number of microvessels in low,medium and high dose groups and cisplatin groups was significantly decreased compared with that in the model control group(P<0.05).Compared with the model control group,the mRNA and relative protein expression levels of NLRP3 and IL-1βin the tumor tissue of nude mice were decreased after different concentrations of curcumin(P<0.05).The higher the curcumin concentration,the more significant the decrease of NLRP3 and IL-1βin nude mouse tumor tissue was(P<0.05).Conclusion The mechanism of curcumin against hepatocellular carcinoma may be related to promoting the cell apoptosis in hepatocellular carcinoma and regulating the expression levels of NLRP3 and IL-1β.