摘要
目的:研究淫羊藿苷调控小鼠胰腺癌皮下移植瘤生长和运动的机制。方法:建立BALB/c小鼠皮下胰腺癌移植瘤模型后,分别给予生理盐水(对照组)、10 mg/kg淫羊藿苷(低剂量组)、20 mg/kg淫羊藿苷(中剂量组)、40 mg/kg淫羊藿苷(高剂量组)、5 mg/kg阿霉素(阿霉素组)腹腔给药干预,干预25 d后取出瘤体,检测瘤体重量和体积,并根据小鼠存活情况绘制生存曲线;TUNEL染色观察瘤组织凋亡情况,免疫组化检测Ki67、血管内皮生长因子(VEGF)蛋白阳性表达率;qRT-PCR检测瘤组织中生长和运动标记分子基因相对表达情况,Western blot检测Wnt/β-catenin和核因子κB(NF-κB)p65信号通路关键蛋白表达情况。结果:与对照组相比,中、高剂量淫羊藿苷及阿霉素干预后,移植瘤的重量、体积,瘤组织中Ki67、VEGF的阳性表达率,Ki67、VEGF、基质金属蛋白酶-9(MMP-9)的mRNA相对表达量,β-catenin蛋白表达量、NF-κB p65蛋白磷酸化水平均显著降低(P<0.05),小鼠的25 d存活率、瘤组织细胞凋亡率以及Caspase-3的mRNA相对表达量均显著升高(P<0.05)。结论:淫羊藿苷可能通过抑制β-catenin和NF-κB p65的活性下调增殖及运动相关基因表达,上调凋亡相关基因表达从而调节小鼠胰腺癌皮下移植瘤的生长和运动。
Objective:To study mechanism of icariin on regulating growth and movement of subcutaneous xenografts in pancreatic cancer mice.Methods:After establishing subcutaneous xenografts models of pancreatic cancer BALB/c mice,they were intraperitoneally administered with normal saline(control group),10 mg/kg icariin(low dose group),20 mg/kg icariin(middle dose group),40 mg/kg icariin(high dose group),and 5 mg/kg doxorubicin(doxorubicin group).At 25d after intervention,tumors were taken out.The tumor weight and volume were measured.The survival curves were drawn by survival conditions of mice.The apoptosis of tumor tissue was observed by TUNEL staining.The positive expression rates of Ki67 and vascular endothelial growth factor(VEGF)protein were detected by immunohistochemistry.The relative expression of growth and movement marker molecules genes in tumor tissue was detected by qRT-PCR.The expression of key proteins in Wnt/β-catenin and nuclear factor-κB(NF-κB)p65 signaling pathway was detected by Western blot.Results:Compared with control group,after intervention with middle and high dose of icariin and doxorubicin,weight and volume of xenografts,positive expression rates of Ki67 and VEGF in tumor tissue,relative expression quantities of Ki67,VEGF and matrix metalloproteinase-9(MMP-9)mRNA,expression quantity ofβ-catenin protein and phosphorylation level of NF-κB p65 protein were significantly decreased(P<0.05),while 25-d survival rate,apoptosis rate of tumor tissue and relative expression quantity of Caspase-3 mRNA were significantly increased(P<0.05).Conclusion:Icariin may down-regulate expression of proliferation and movement related genes,and up-regulate expression of apoptosis related genes by inhibiting activity ofβ-catenin and NF-κB p65,thus regulating growth and movement of subcutaneous xenografts in pancreatic cancer mice.
作者
代云龙
吴礼国
章志军
欧扬
黄俊伟
彭兵
DAI Yun-Long;WU Li-Guo;ZHANG Zhi-Jun;OU Yang;HUANG Jun-Wei;PENG Bing(Department of Hepatobiliary Surgery,Wenjiang District People′s Hospital,Wenjiang 611130,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2020年第3期343-348,共6页
Chinese Journal of Immunology
基金
四川省卫生和计划生育委员会2015年科研课题(No.150033)
