预知子联合雷公藤红素对肝癌荷瘤裸鼠的抑瘤作用及对NF-κB通路的影响  

Antitumor Effect of Akebia Fructus Combined with Celastrol on Hepatoma Bearing Nude Mice and Its Influence on NF-κB Pathway

作　　者：张夜航 彭佩克 方肇勤[1] 卢文丽[1] ZHANG Yehang;PENG Peike;FANG Zhaoqin;LU Wenli(College of Basic Medical Science,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学基础医学院,上海201203

出　　处：《中国中医药信息杂志》2022年第9期95-100,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(82004000、81873212);上海市进一步加快中医药事业发展三年行动计划[ZY(2018-2020)-CCCX-2001-01]。

摘　　要：目的 观察预知子联合雷公藤红素对肝癌荷瘤裸鼠的抑瘤作用及对核因子(NF)-κB通路的影响,并探讨其作用靶点。方法 皮下接种肝癌SMMC7721细胞建立荷瘤裸鼠模型,将裸鼠随机分为模型对照组、预知子提取物组、雷公藤红素组和联合组,将药物包载于壳聚糖/甘油磷酸钠温敏性凝胶系统,分别于分组后第1、6、11日经皮瘤内注射相应药物,共3次。每2日测量裸鼠体质量和瘤径,第16日称量瘤体及肝、脾、左肾脏器质量,计算瘤指数、抑瘤率及脏器指数;ELISA测定血清肿瘤坏死因子(TNF)-α含量;HE染色观察瘤组织形态变化;Western blot检测瘤组织NF-κB通路相关蛋白表达。结果 与模型对照组比较,各给药组裸鼠体质量、去瘤体质量、瘤体积、瘤质量和瘤指数均呈下降趋势,其中以雷公藤红素组最为显著(P<0.05),联合组瘤体积和瘤质量显著下降(P<0.05),各给药组裸鼠肝和左肾质量及指数均显著下降(P<0.05),预知子提取物组、雷公藤红素组和联合组抑瘤率分别为6.68%、35.08%和22.00%;各给药组裸鼠血清TNF-α含量显著增加(P<0.05);HE染色显示,各给药组裸鼠瘤组织均出现间质增多现象,且联合组部分区域出现炎症细胞浸润、堆积;Western blot结果显示,雷公藤红素组裸鼠瘤组织IκB激酶α(IKKα)、周期蛋白依赖性激酶2(CDK2)、周期蛋白D1(Cyclin D1)、NF-κB p65蛋白表达显著降低(P<0.05),联合组裸鼠瘤组织NF-κB抑制蛋白α(IκBα)和p-IκBα蛋白表达显著降低(P<0.05)。结论 预知子联合雷公藤红素能抑制肝癌荷瘤裸鼠肿瘤生长,NF-κB通路p-IκBα分子可能是二者联合发挥抑瘤作用的重要靶点。Objective To observe the anti-tumor effect of Akebia Fructus combined with celastrol on hepatoma bearing nude mice and its effects on NF-κB pathway;To discuss its target. Methods Subcutaneous inoculation of liver cancer SMMC7721 cells was used to establish a tumor-bearing nude mouse model. The nude mice were randomly divided into model control group, extract of Akebia Fructus group, celastrol group and combination group.The drugs were encapsulated in a chitosan/sodium glycerophosphate thermosensitive gel system, and were administered via intratumoral injection on the 1st, 6th, and 11th days after grouping, for a total of 3 times. The body mass and tumor diameter of nude mice were measured every 2 days. On the 16th day, the tumor body and the mass of liver, spleen and left kidney were weighed, and the tumor index, tumor inhibition rate and organ index were calculated;the content of serum tumor necrosis factor-α(TNF-α) was determined by ELISA;the morphological changes of tumor tissue were observed by HE staining;the expression of NF-κB pathway-related proteins in tumor tissue were detected by Western blot. Results Compared with the model control group, there was a down trend of the body mass, tumor-removed body mass, tumor volume, tumor mass and tumor index of each administration group,and the celastrol group was the most significant(P<0.05), the tumor size and tumor mass in the combination group significantly decreased(P<0.05), the liver and left kidney mass and index in each administration group were significantly decreased(P<0.05), and the tumor inhibition rates of extract of Akebia Fructus group, celastrol group and combination group were 6.68%, 35.08% and 22.00% respectively;the content of serum TNF-α in each administration group increased(P<0.05);HE staining showed that the tumor tissue of nude mice in each administration group showed increased interstitial phenomenon, and the infiltration and accumulation of inflammatory cells appeared in some areas of the combination group;Western blot results showed t

关 键 词：预知子 雷公藤红素 肝癌 裸鼠 NF-ΚB通路 

分 类 号：R285.5[医药卫生—中药学]