石上柏颗粒对肝癌模型小鼠瘤组织中Cyclin D1、CKS表达的影响
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摘要
目的:研究石上柏颗粒对肝癌模型小鼠瘤组织中Cyclin D1、CKS表达的影响。方法:选取48只肝癌模型小鼠,随机分为为模型组、氟尿嘧啶组、石上柏颗粒组、联合给药组,每组各12例。氟尿嘧啶组给予氟尿嘧啶20 mg·kg~(-1)灌胃,石上柏颗粒组给予石上柏颗粒120 mg·kg~(-1)灌胃,联合给药组同时灌胃氟尿嘧啶20 mg·kg~(-1)和石上柏颗粒120mg·kg~(-1),模型组小鼠给予同体积纯净水,各组小鼠连续灌胃不同药物4周,比较各组小鼠治疗期间肿瘤生长情况,采用RT-PRC法测定各组小鼠瘤组织中Cyclin D1 mRNA、CKS mRNA的表达,采用West-blot法测定瘤组织中Cyclin D1、CKS蛋白的表达。结果:(1)给药1周、2周、3周、4周时氟尿嘧啶组小鼠移植瘤体积均较模型组小鼠显著降低(P<0.05),给药2周、3周、4周时石上柏颗粒组小鼠移植瘤体积均较模型组小鼠显著降低(P<0.05),给药3周、4周时联合给药组移植瘤体积均较氟尿嘧啶组小鼠显著降低,差异有统计学意义(P<0.05);(2)给药4周时氟尿嘧啶组、石上柏颗粒组和联合给药组小鼠瘤组织Cyclin D1 mRNA、CKS mRNA均较模型组显著降低(P<0.05),而联合给药组小鼠瘤组织Cyclin D1mRNA、CKS mRNA较氟尿嘧啶组显著降低,差异有统计学意义(P<0.05);(3)给药4周时,氟尿嘧啶组、石上柏颗粒组和联合给药组小鼠瘤组织Cyclin D1和CKS蛋白均较模型组显著降低(P<0.05),而联合给药组小鼠瘤组织Cyclin D1和CKS蛋白较氟尿嘧啶组显著降低,差异有统计学意义(P<0.05)。结论:石上柏颗粒有显著抗肝癌作用,且可以增强氟尿嘧啶的疗效,其抗肝癌作用可能与其抑制Cyclin D1和CKS表达有关。
Objective:To study the effect of Selaginella granule on the expression of Cyclin D1 and CKS in tumor tissues of mice with hepatocellular carcinoma.Methods:Forty-eight HCC mice were randomly divided into model group,fluorouracil group,Selaginella granule group and combined group,with 12 cases in each group.The rats in the fluorouracil group were treated with fluorouracil 20 mg·kg~(-1),and the rats in Selaginella granule group were treated with Selaginella granule 120 mg·kg~(-1).The rats in the combined group were given both medications.The mice in the model control group were given the same volume of pure water.The mice of each group were treated with different drugs for 4 weeks.The tumor growth was analyzed.The expressions of Cyclin D1mRNA and CKS mRNA in the tumor tissue of each group were measured with RT-PRC method.The expression of Cyclin D1 and CKS protein in tumor tissue was detected with West-blot.Results:(1)The volume of transplanted tumor in the fluorouracil group was significantly lower than that in the model group(P<0.05)at 1 week,2 weeks,3 weeks and 4 weeks(P<0.05).The volume o transplanted tumor in the Selaginella granule group was significantly lower than that in the fluorouracil group at 3 weeks and 4weeks(P<0.05).(2)The expression of Cyclin D1 mRNA and CKS mRNA in the fluorouracil group,the Selaginella granule group and the combined administration group were significantly lower than those in the model group(P<0.05).(3)Four weeks after administration,the levels of Cyclin D1 mRNA and CKS mRNA in the fluorouracil group,the Selaginella granule group and the combined administration group were significantly lower than those in the model group.The expression of Cyclin D1 and CKS in the tumor tissue of the mice was significantly lower than that of the model group(P<0.05),but the expression of Cyclin D1 and CKS protein in the combined group was significantly lower than that in the fluorouracil group(P<0.05).Conclusion:Selaginella granule has a significant anti-hepatocarcinoma effect,and it can enhance the efficacy of fluorouracil.Its anti-hepatoma effect may be related to its inhibition the expression of Cyclin D1 and CKS.
Objective:To study the effect of Selaginella granule on the expression of Cyclin D1 and CKS in tumor tissues of mice with hepatocellular carcinoma.Methods:Forty-eight HCC mice were randomly divided into model group,fluorouracil group,Selaginella granule group and combined group,with 12 cases in each group.The rats in the fluorouracil group were treated with fluorouracil 20 mg·kg~(-1),and the rats in Selaginella granule group were treated with Selaginella granule 120 mg·kg~(-1).The rats in the combined group were given both medications.The mice in the model control group were given the same volume of pure water.The mice of each group were treated with different drugs for 4 weeks.The tumor growth was analyzed.The expressions of Cyclin D1mRNA and CKS mRNA in the tumor tissue of each group were measured with RT-PRC method.The expression of Cyclin D1 and CKS protein in tumor tissue was detected with West-blot.Results:(1)The volume of transplanted tumor in the fluorouracil group was significantly lower than that in the model group(P<0.05)at 1 week,2 weeks,3 weeks and 4 weeks(P<0.05).The volume o transplanted tumor in the Selaginella granule group was significantly lower than that in the fluorouracil group at 3 weeks and 4weeks(P<0.05).(2)The expression of Cyclin D1 mRNA and CKS mRNA in the fluorouracil group,the Selaginella granule group and the combined administration group were significantly lower than those in the model group(P<0.05).(3)Four weeks after administration,the levels of Cyclin D1 mRNA and CKS mRNA in the fluorouracil group,the Selaginella granule group and the combined administration group were significantly lower than those in the model group.The expression of Cyclin D1 and CKS in the tumor tissue of the mice was significantly lower than that of the model group(P<0.05),but the expression of Cyclin D1 and CKS protein in the combined group was significantly lower than that in the fluorouracil group(P<0.05).Conclusion:Selaginella granule has a significant anti-hepatocarcinoma effect,and it can enhance the efficacy of fluorouracil.Its anti-hepatoma effect may be related to its inhibition the expression of Cyclin D1 and CKS.
引文
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[11]张有福,董秀山,闫曙光,等.熊去氧胆酸对大鼠肝再生和细胞周期蛋白D1表达的影响[J].中华实验外科杂志,2010,27(7):898-899.
[12]Lassmann S,Schuster I,Walch A,et al.STAT3 mRNA and protein expression in colorectal cancer:effects on STAT3-inducible targets linked to cell survival and proliferation[J].J Clin Pathol,2007,60(2):173-179.
[13]Lee EK,Kim DG,Kim JS,et al.Cell-cycle regulator Cksl promotes hepatocellular carcinoma by supporting NF-KB-dependent expression of interleukin-8[J].Cancer Res,2011,7l(21):6827-6835.
[14]刘晓丽,马礼鸿,王全义.乳腺癌组织中CKSl和Cyclin D1的表达及相关分析[J].重庆医科大学学报,2013,38(1):54-57.
[15]张秀梅,顾金松,刘曙,等.Cks1在老年肝细胞癌中的表达及临床意义[J].中国肿瘤外科杂志,2013,5(4):239-240.
[2]郑剑霄,周同冲,徐凯,等.石上柏联合放疗治疗鼻咽癌临床观察[J].南方医科大学学报,2006,26(2):247-248.
[3]方玉春,朱伟明,管永光,等.鱼藤、枫桦和石上柏的细胞毒及抗氧化活性初步研究[J].中国海洋大学学报,2008,38(3):401-403.
[4]黄建勇,李少光,李宇翔,等.石上柏抗肿瘤活性部位及其化学成分研究[J].福建医科大学学报,2013,47(1):1-5.
[5]Forner A,Llovet JM,Bruix J.Hepatocellular carcinoma[J].Lancet,2012,379(9822):1245-1255.
[6]Ferlay J,Shin HR,Bray F,et al.Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008[J].International journal of cancer,2010,127(12):2893-2917.
[7]樊嘉,王征.肝移植治疗原发性肝癌的现状[J].肝胆外科杂志,2011,19(5):321-323.
[8]Zhang CY,Huang TR,Yu JH,et al.Epidemiological analysis of primary liver cancer in the early 21st century in Guangxi province of China[J].Chinese J Cancer,2010,29(5):545-550.
[9]Sun Y,Yang H,Mao Y,et al.Increased Golgi protein 73 expression inhepatocellular carcinoma tissue correlates with tumor aggression but not surviva1[J].J Gastroenteml Hepatol,2011,26(7):1207-1212.
[10]Hou J,Wang D,Zhang R,et al.Experimental therapy of hepatoma with artemisinin and its derivatives:in vitro and in vivo activity,chemosensitization,and mechanisms of action[J].Clin Cancer Res,2008,14(17):5519-5530.
[11]张有福,董秀山,闫曙光,等.熊去氧胆酸对大鼠肝再生和细胞周期蛋白D1表达的影响[J].中华实验外科杂志,2010,27(7):898-899.
[12]Lassmann S,Schuster I,Walch A,et al.STAT3 mRNA and protein expression in colorectal cancer:effects on STAT3-inducible targets linked to cell survival and proliferation[J].J Clin Pathol,2007,60(2):173-179.
[13]Lee EK,Kim DG,Kim JS,et al.Cell-cycle regulator Cksl promotes hepatocellular carcinoma by supporting NF-KB-dependent expression of interleukin-8[J].Cancer Res,2011,7l(21):6827-6835.
[14]刘晓丽,马礼鸿,王全义.乳腺癌组织中CKSl和Cyclin D1的表达及相关分析[J].重庆医科大学学报,2013,38(1):54-57.
[15]张秀梅,顾金松,刘曙,等.Cks1在老年肝细胞癌中的表达及临床意义[J].中国肿瘤外科杂志,2013,5(4):239-240.