胡椒碱对DMH/DSS诱导实验性结肠癌变的影响及其机制  

Effects of piperine on experimental colon carcinogenesis induced by DMH/DSS and its mechanism

作　　者：李忆东 李婷婷[1] 赵珠峰[1] 吴国忠 Li Yidong;Li Tingting;Zhao Zhufeng;Wu Guozhong(Department of Basic Medicine,School of International Medical Technology,Shanghai Shanda University,Shanghai 201209,China)

机构地区：[1]上海杉达学院国际医学技术学院基础医学部,上海201209

出　　处：《中国医师杂志》2022年第10期1493-1497,1503,共6页Journal of Chinese Physician

基　　金：上海杉达学院护理学重点学科重点立项课题(2019zz35-yj)

摘　　要：目的探讨胡椒碱对1,2-二甲基肼(DMH)/右旋糖酐硫酸钠(DSS)诱导实验性结肠癌肿瘤细胞生长和增殖的影响及其具体机制。方法将36只小鼠分为对照组、模型组和胡椒碱组,每组12只。对照组给予生理盐水灌胃;模型组和胡椒碱组通过DMH/DSS复合法建立实验性结肠癌模型后分别给予生理盐水和胡椒碱3.6 mg/(kg·d)灌胃。观察肿瘤负荷和体积,HE染色法观察小鼠结肠的组织学变化,蛋白免疫印迹法(Western blot)检测RAS/PI3K/AKT相关通路蛋白的表达。结果模型组体重增加值及cleaved PARP、cleaved caspase-3表达水平均显著低于对照组(均P<0.05),Bcl-2、Bax、pan-RAS、p-MEK、p-ERK、PI3K、p-AKT、NF-κBp65、c-Myc、cyclin D1蛋白表达水平均显著高于对照组(均P<0.05)。胡椒碱组体重增加值及cleaved PARP、cleaved caspase-3表达水平均显著高于模型组(均P<0.05);Bcl-2、Bax、pan-RAS、p-MEK、p-ERK、PI3K、p-AKT、NF-κBp65、c-Myc、cyclin D1蛋白表达水平均显著低于模型组(均P<0.05)。结论胡椒碱对DMH/DSS诱导的实验性结肠癌发生具有抑制作用,其抑制作用可能涉及到RAS/PI3K/AKT信号轴。Objective To investigate the effects of piperine on experimental colon carcinogenesis induced by 1,2-dimethylhydrazine(DMH)/sodium dextran sulfate(DSS)and its mechanism.Methods 36 mice were divided into control group,model group and piperine group,12 mice in each group.The control group was given normal saline by gavage;The model group and piperine group were given 3.6 mg/(kg·d)of normal saline and piperine respectively after establishing the experimental colon cancer model induced by DMH/DSS.Tumor load and volume were observed.Hematoxylin and eosin(HE)staining was used to observe the histological change of colon in mice.RAS/PI3K/AKT related pathway protein expression was detected by Western blot.Results The body weight gain,protein expression levels of cleaved poly-ADP ribose polymerase(PARP),cleaved caspase-3 in model group were significantly lower than those in the control group(all P<0.05).The protein expression levels of Bcl-2,Bax,pan-Ras,p-MEK,p-ERK,PI3K,p-AKT,NF-κBP65,c-Myc and cyclin D1 in model group were significantly higher than those in the control group(all P<0.05).The body weight gain,protein expression levels of cleaved PARP and cleaved caspase-3 in piperine group were significantly higher than those in model group(all P<0.05).The protein expression levels of Bcl-2,Bax,pan-Ras,p-MEK,p-ERK,PI3K,p-AKT,NF-κBP65,c-Myc and cyclin D1 in piperine group were significantly lower than those in model group(all P<0.05).Conclusions Piperine can inhibit the occurrence of experimental colon cancer induced by DMH/DSS,which may involve multiple components of RAS/PI3K/AKT signal axis.

关 键 词：结直肠肿瘤 胡椒碱 RAS/PI3K/AKT信号轴 二甲基肼 右旋糖酐硫酸钠 

分 类 号：R73[医药卫生—肿瘤]