姜黄素对乳腺癌小鼠肿瘤组织的抑制作用及其机制  

Inhibitory effect and mechanism of curcumin on tumor tissues of breast cancer mice

作　　者：宋波[1] 高波[1] Song Bo;Gao Bo(Department of Breast Surgery,Gansu Cancer Hospital,Lanzhou 730050,China)

机构地区：[1]甘肃省肿瘤医院乳腺外科,兰州730050

出　　处：《中华实验外科杂志》2019年第9期1579-1582,共4页Chinese Journal of Experimental Surgery

基　　金：甘肃省卫生行业科研计划项目(GSWSKY2018-07).

摘　　要：目的探讨姜黄素对乳腺癌小鼠的抗肿瘤作用及其机制.方法将4T1小鼠乳腺癌细胞接种于BALB/c小鼠乳腺脂肪垫下,建立乳腺癌小鼠模型.将成功建模的荷瘤小鼠随机分为模型组和姜黄素低、中、高剂量(25、50、100 mg/kg)组.连续给药4周后,计算抑瘤率、脾脏指数和胸腺指数;酶联免疫吸附试验(ELISA)法检测血清中白细胞介素-2(IL-2)、白细胞介素-12(IL-12)和肿瘤坏死因子-α(TNF-α)含量;蛋白质印迹法(Western blot)检测肿瘤组织中磷脂酰肌醇3激酶(PI3K)、丝氨酸-苏氨酸蛋白激酶(Akt)和哺乳动物雷帕霉素靶蛋白(mTOR)蛋白表达及磷酸化水平.细胞计数试剂盒-8(CCK-8)法检测PI3K激动剂胰岛素样生长因子(IGF-1)、抑制剂LY294002和姜黄素对小鼠乳腺癌细胞4T1的影响,并探讨IGF-1、LY294002和姜黄素对MCF-7细胞PI3K/Akt/mTOR信号通路的影响.应用SPSS 17.0统计软件分析,多组间比较采用单因素方差分析,两组间比较采用独立样本t检验.结果姜黄素中、高剂量组肿瘤重量[(0.91±0.21)、(0.83±0.18)比(1.18±0.24)g,t=2.820,P<0.05;t=3.846,P<0.01]低于模型组,抑瘤率分别为22.88%和29.66%.姜黄素中、高剂量组脾脏指数[(7.14±0.85)、(7.58±0.89)比(6.32±0.57)mg/g,t=2.398,P<0.05;t=3.628,P<0.01]和高剂量组胸腺指数[(2.85±0.47)比(2.33±0.28)mg/g,t=3.254,P<0.01]高于模型组.姜黄素中、高剂量组血清IL-2[(139.55±16.95)、(146.78±17.21)比(120.46±15.45)ng/L,t=2.819,P<0.05;t=3.859,P<0.01]、TNF-α[(53.46±6.89)、(57.19±7.01)比(46.57±6.32)ng/L,t=2.493,P<0.05;t=3.811,P<0.01]和高剂量组IL-12[(163.24±18.73)比(148.26±16.31)ng/L,t=2.340,P<0.05]高于模型组.姜黄素中、高剂量组肿瘤组织中p-Akt水平(0.69±0.12、0.62±0.08比0.83±0.14,t=2.405,P<0.05;t=4.161,P<0.01)和高剂量组p-PI3K(0.62±0.11比0.75±0.13,t=2.537,P<0.05)、p-mTOR(0.56±0.11比0.69±0.17,t=2.098,P<0.05)水平低于模型组.IGF-1、LY294002和姜黄素(100μmo]/L)干预4T1后,细胞存活率分别为21Objective To study the anti-tumor effect of curcumin on breast cancer mice and its mechanism.Methods 4T1 mouse breast cancer cells were inoculated into mammary at pad of BALB/c mice for establishing the breast cancer mouse model.The tumor-bearing mice were divided into model group and curcumin low,medium and high dose(25,50,100 mg/kg)group.After 4 weeks of continuous administration,the tumor inhibition rate,spleen index and thymus index were calculated.The serum contents of interleukin-2(IL-2),interleukin-12(IL-12)and interleukin-α(TNF-α)were detected by enzyme-linked immunosorbent assay.The protein expression of phosphoinositide 3-kinase(PI3K),serine-threonine kinase(Akt),mammalian target of rapamycin(mTOR)and phosphorylation levels were detected by Western blotting.The effects of insulin-like growth factors-1(IGF-1)which could activate PI3K,LY294002 which could inhibit PI3K and curcumin on the activity of mouse breast cancer cell 4T1 was detected by CCK-8 method,and to explore the effects of IGF-1,LY294002 and curcumin on PI3K/Akt/mTOR signaling pathway in 4T1 cells.Measurement data were expressed as Mean±SD,and t-test was used for comparison between groups.Results The tumor weight[(0.91±0.21),(0.83±0.18)vs.(1.18±0.24)g,t=2.820,P<0.05;t=3.846,P<0.01]of curcumin medium,high dose groups was lower than model group,and the tumor inhibition rate was 22.88%and 29.66%.The spleen index[(71.37±8.54),(75.79±8.87)vs.(63.21±5.74)mg/10 g,t=2.398,P<0.01;t=3.628,P<0.01 of curcumin medium,high dose groups and the thymus index[(28.46±4.74)vs.(23.33±2.78)mg/10g,t=3.254,P<0.01]of high dose group were higher than model group.The serum IL-2 contents[(139.55±16.95),(146.78±17.21)vs.(120.46±15.45)ng/L,t=2.819,P<0.05;t=3.859,P<0.01]and TNF-αcontents[(53.46±6.89),(57.19±7.01)vs.(46.57±6.32)ng/L,t=2.493,P<0.05;t=3.811,P<0.01]of curcumin medium,high dose groups,and IL-12 contents[(163.24±18.73)vs.(148.26±16.31)ng/L,t=2.340,P<0.05]of high dose group were higher than model group.The p-Akt levels in tumor tissue[(0.69±0

关 键 词：姜黄素 小鼠乳腺癌 磷脂酰肌醇3激酶/丝氨酸-苏氨酸蛋白激酶/哺乳动物雷帕霉素靶蛋白信号通路 

分 类 号：R285.5[医药卫生—中药学]