文献类型：期刊文献

中文题名：黄芪总皂苷联合顺铂对H22荷瘤小鼠STAT3介导的炎症信号通路的抑制作用

英文题名：Inhibition Effects of Total Astragalosides Combined with Cisplatin on STAT3-mediated Inflammatory Signal Pathways in H Tumor-bearing Mice

作者：颜春鲁[1];骆亚莉[2];安方玉[3];刘雪松[4];刘永琦[5];汪永锋[6];贺娟娟[7];潘婷[7];赵崇博[7]

第一作者：颜春鲁

机构：[1]甘肃中医药大学中医临床学院中医骨伤教研室,兰州730000;[2]甘肃中医药大学基础学院病理生理教研室,兰州730000;[3]甘肃中医药大学教学实验实训中心生物化学实验室,兰州730000;[4]甘肃中医药大学基础医学院生物化学教研室,兰州730000;[5]甘肃中医药大学基础医学院免疫教研室,兰州730000;[6]甘肃中医药大学基础医学院解剖教研室,兰州730000;[7]甘肃中医药大学临床医学院内科学教研室,兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2020

卷号：36

期号：11

起止页码：1359

中文期刊名：中国生物化学与分子生物学报

外文期刊名：Chinese Journal of Biochemistry and Molecular Biology

收录：CSTPCD;;北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；PubMed;

基金：甘肃省科技支撑计划(1204FKCA169);甘肃省高校大学生就业创业能力提升工程项目(6-1);甘肃中医药大学教学研究与教学改革项目(ZH-201606)。

语种：中文

中文关键词：肝癌;黄芪总皂苷;顺铂;白细胞介素-6/信号转导和转录激活因子3信号通路

外文关键词：liver cancer;Total Astragalosides;cisplatin;IL-6/STAT3 signal pathway

摘要：本研究前期证实,黄芪总皂苷通过增强机体的免疫力发挥抑制H22荷瘤小鼠肿瘤生长的作用,但其具体的抗瘤分子机制尚不明确,并且与治肝癌的化疗药物顺铂是否具有协同作用,目前尚未见报道。为探讨黄芪总皂苷联合顺铂对H22荷瘤小鼠的抗瘤机制,本研究以小鼠肝癌H22移植瘤模型为研究对象,随机分为模型组、黄芪总皂苷治疗组、顺铂治疗组、黄芪总皂苷联合顺铂治疗组,另设空白对照组,每组10只。各组小鼠接瘤24 h后,给予相应药物干预。干预10 d后,采用HE染色、ELISA法、免疫组化染色,对H22荷瘤小鼠的肿瘤组织病理形态、细胞因子及凋亡蛋白质等指标进行检测。结果显示,模型组小鼠可见肿瘤细胞生长密集,细胞出现明显的异型性和病理性核分裂像,其血清IL-6含量明显升高(P<0.01);各治疗组肿瘤细胞出现大片凝固性坏死,各治疗组瘤体质量均明显降低(P<0.05或P<0.01),黄芪总皂苷联合顺铂组的抑瘤率高于单用黄芪总皂苷组和顺铂组的抑瘤率(P<0.05),联合用药疗效具有相加效应;各治疗组小鼠血清IL-6含量明显降低,其肿瘤组织STAT3和存活蛋白素(survivin)的蛋白的表达水平明显下降,胱天蛋白酶-3(caspase-3)蛋白的表达水平明显升高(P<0.05或P<0.01),以LH组作用最为明显。以上结果表明,黄芪总皂苷联合顺铂对H22荷瘤小鼠的抑瘤机制可能与抑制STAT3信号通路中IL-6的含量,以及存活蛋白素Survivin蛋白的表达水平和上调,胱天蛋白酶-3 caspase-3蛋白的表达水平有关。其结果阐释了黄芪总皂苷联合顺铂可能的抗瘤机制,为开发安全、有效的抗肿瘤药物提供实验依据。
Total Astragalosides has been shown to have inhibitory effects on the tumor growth of H22 tumor-bearing mice by enhancing immunity,but the specific molecular mechanism is still unclear,and it has not been reported whether it has synergistic effects with cisplatin.To investigate the antitumor mechanism of Total Astragalosides combined with cisplatin in H22 tumor-bearing mice,H22 hepatoma tumor-bearing mice were used as experimental subjects.A total of 40 H22 hepatocarcinoma model mice were randomly divided into the model group,Total Astragalosides group,cisplatin group and Total Astragalosides combined with the cisplatin group.Another control group was set up,with ten mice in each group.After inoculation of H22 hepatoma cells for 24 hours,the mice in each group were given the corresponding drug intervention.After 10 intervention days,HE stain,ELISA methods,immunohistochemistry assays were used to study the pathologies of tumor tissues,cytokines and apoptosis proteins of mice.The results showed that the tumor cellularity,atypia and irregular mitosis of the model group were significantly increased,serum levels of IL-6 in the model group was also increased(P<0.01).The massive necrosis of tumor cells appeared in the treatment group,the mass of tumor was decreased in the Total Astragalosides group,cisplatin group and Total Astragalosides combined with the cisplatin group(P<0.05 or P<0.01),the tumor inhibiting rate of Total Astragalosides combined with cisplatin group was better than that of both Total Astragalosides group and cisplatin group(P<0.05),suggesting that Total Astragalosides combined with cisplatin had cooperative effects.The serum level of IL-6 was declined in the Total Astragalosides group,cisplatin group and Total Astragalosides combined with cisplatin group,the protein expression of STAT3 and survivin in tumour tissues was decreased and the protein expression of caspase-3 in tumor tissues was increased in the Total Astragalosides group,cisplatin group and Total Astragalosides combined with cisplatin group(P<0.05 or P<0.01),with the Total Astragalosides combined with cisplatin group being the most obvious,suggesting that the anti-tumor mechanism of Total Astragalosides may be related to reducing the levels of IL-6,survivin and increasing the level of caspase-3 of the STATS signal pathway and the improvement of hippocampal white matters in mice.The results elucidated the possible anti-tumor mechanism of Total Astragalosides combined with cisplatin,and provided experimental basis for the development of safe and effective anti-tumor drugs.