昆参颗粒对S180荷瘤小鼠C-myc、P16蛋白表达及P16基因甲基化的影响  

Effects of Kunshen Granule on the expression of C-myc,P16 and methylation of P16 gene in S180 tumor-bearing mice

作　　者：王晓妍[1] 曹志群[1] 

机构地区：[1]山东中医药大学,山东济南250014

出　　处：《时珍国医国药》2015年第7期1550-1552,共3页Lishizhen Medicine and Materia Medica Research

基　　金：国家科技重大专项(2009ZX09502-015);国家自然科学基金(30973826);高校博士点基金项目(20093731110004)

摘　　要：目的研究昆参颗粒对S180荷瘤小鼠C-myc、P16蛋白表达及P16基因甲基化的影响。方法将昆明种小鼠60只以数字表法随机分为模型对照组、参莲胶囊组、昆参大、小剂量组,每组15只。全部小鼠于右侧腋窝下接种S180瘤株,每鼠0.2ml。各组在接种瘤株后第3天进行灌胃给药,每日1次。昆参大剂量组(昆参颗粒800mg/kg)、昆参小剂量组(昆参颗粒400mg/kg)、参莲胶囊组(参莲胶囊600mg/kg)、模型对照组以等量生理盐水灌胃。第12天处死所有小鼠,剥离肿瘤组织。Methylight法检测小鼠胃癌组织P16基因甲基化。免疫组织化学(S-P法)测定肿瘤组织中C-myc、P16蛋白表达。结果与模型对照组比较,昆参颗粒能明显抑制P16基因的甲基化、提升P16蛋白表达水平(P<0.05)。昆参颗粒抑制P16基因的甲基化、增加P16蛋白表达的作用优于参莲胶囊,且随剂量的增加而增大。昆参颗粒对C-myc蛋白表达的抑制作用随剂量的增加而增大。以上结果显示:昆参颗粒能明显抑制P16基因的甲基化、提升P16蛋白表达水平并抑制C-myc蛋白表达,存在一定的量效关系,起效剂量为400mg/kg。小鼠胃组织中P16与C-myc蛋白表达呈负相关(P<0.05)。结论昆参颗粒可抑制P16基因的甲基化,提高胃癌组织P16蛋白的表达水平,同时抑制C-myc蛋白表达可能是其发挥抗肿瘤功效的重要机制。Objective To study the effect of Kunshen Granule on the expression of C- myc,P16 and methylation of P16 gene in S180 tumor- bearing mice.Methods 60 S180 tumor- bearing mice were separated into four groups at random,negative control group,Shenlian Capsule group,Kunshen high dose group and low dose group.There were 15 mice in each group.Planting S180 cells in all mice right armpit,each mouse 0.2ml.All groups were administrated orally in third days after planting tumor cells,one time a day.Kunshen high dose group（ Kunshen Granule 800 mg / kg）,Kunshen low dose group（ Kunshen Granule 400 mg / kg）,Shenlian Capsule group（ Shenlian Capsule 600 mg / kg）,negative control group with normal saline lavage.Twelfth days all mice were killed,the tumor tissue was stripping.Detection of P16 gene promoter in gastric cancer tissue in mice by Methylight.The expression of C- myc and P16 was determined by immunohistochemistry（ SP method）.Results Compared with negative control group,Kunshen Granule can obviously inhibit methylation of P16 gene and improve the expression level of P16 protein,with statistical difference（ P〈0.05）; compared with Shenlian capsule group,Kunshen granule can obviously inhibit methylation of P16 gene and improve the expression level of P16 protein,and the effect with the dose increase.Kunshen granule can obviously inhibit the expression of C- myc protein,and the effect with the dose increase.The results show that Kunshen granule can obviously inhibit methylation of P16 gene,improve the expression level of P16 protein and inhibit the expression of C- myc protein,and the effect with the dose increase,effective dose is 400 mg / kg.The expression of P16 and C- myc is negatively correlated（ P〈0.05）.Conclusion Kunshen Granule could inhibit methylation of P16 gene,increase P16 expression and inhibit the expression levels of C- myc in gastric carcinoma tissue,that may play the important mechanism of anti- tumor effect.

关 键 词：昆参颗粒 S180荷瘤小鼠 基因甲基化 蛋白表达 

分 类 号：R285.5[医药卫生—中药学]