丹参酮ⅡA纳米粒对肝癌小鼠p38MAPK、TGFβ_1及Cyclin E蛋白表达的影响

Influence of tanshinone ⅡA nanoparticles on the expressions of p38MAPK,TGFβ_1 and Cyclin E proteins in mice with hepatic cancer

目的观察丹参酮ⅡA纳米粒对肝癌小鼠p38有丝分裂原活化蛋白激酶(p38MAPK)、转化生长因子β1(TGFβ1)及细胞周期素E(Cyclin E)蛋白表达的影响。方法 60只小鼠制备肝癌模型后随机分为6组,分别给予生理盐水以及等体积的空白纳米粒、丹参酮ⅡA、不同剂量丹参酮ⅡA纳米粒。观察各组肿瘤抑制率及p38MAPK、TGFβ1、Cyclin E蛋白的表达。结果各给药组瘤体质量均较对照组显著缩小(P<0.01),且高剂量组肿瘤抑制率显著高于丹参酮ⅡA组及低剂量组(P<0.01);给药后各给药组p38MAPK、TGFβ1及Cyclin E阳性表达率均显著高于或低于对照组及空白载体组(P<0.01),各剂量丹参酮ⅡA纳米粒组与丹参酮ⅡA组差异显著(P<0.01),且随着剂量增加,表达水平呈现逐步升高或降低趋势,组间差异显著(P<0.01)。结论丹参酮ⅡA纳米粒较丹参酮ⅡA具有更显著的抗肿瘤功效,可能与上调p38MAPK蛋白表达,下调TGFβ1及Cyclin E蛋白表达有关。

Objective To observe the influence of tanshinone ⅡA nanoparticles on the expressions of p38 mitosis mitogen-activated protein kinase（ p38MAPK）,transforming growth factor β1（ TGFβ1） and Cyclin E proteins in mice with hepatic cancer. Methods A total of 60 established mice models with hepatic cancer were randomly divided into 6 groups and respectively treated with normal saline and equivoluminal blank nanoparticles,tanshinone ⅡA and different-concentrations of tanshinone ⅡA nanoparticles. Tumor inhibiting rates and expressions of p38 MAPK,TGFβ1and Cyclin E proteins in both groups were observed. Results The tumor body mass decreased significantly in each drug-treated group than in control group（ P〈0. 01）,and the high-dose group was significantly higher than tanshinone ⅡA group and low-dose group in tumor inhibiting rate（ P〈0. 01）. After drug administration,the positive expression rates of p38 MAPK,TGFβ1and Cyclin E proteins in each drug-treated group were significantly higher or lower than the control group or blank vector group（ P〈0. 01）. In addition,there were significant differences between each dose groups and tanshinone ⅡA group（ P〈0. 01）,and their expression levels showed gradually increasing or decreasing trend along with the increase of Tanshinone Ⅱ A dose,and the differences among groups were significant（ P 0. 0 1）.Conclusion Tanshinone ⅡA nanoparticles are more effective than tanshinone ⅡA in treatment of tumor,which is associated with up-regulating the expression of p38 MAPK protein and down-regulating the expressions of TGFβ1and Cyclin E proteins.