乳岩宁联合依西美坦对荷瘤裸鼠抑瘤机制的研究

Study the mechanism on cancer inhibition of Chinese herbal compound Ruyanning combined exemestane on breast tumor bearing nude mice

目的探究乳岩宁联合依西美坦对乳腺癌荷瘤裸鼠抑制肿瘤细胞生长的机制。方法建立乳腺癌(MDA-MB-435)荷瘤裸鼠模型后,分为模型对照组、乳岩宁组、依西美坦组、联合组(依西美坦+乳岩宁组),每天灌药一次,持续21 d。取材,称取各组瘤体质量。采用Western blotting法测定各组p53和HIF-1蛋白的表达。采用实时荧光定量RT-PCR法检测各组PI3K、AKT、NF-KB基因表达。结果瘤体质量:与对照组比较,乳岩宁组、依西美坦组和联合组的瘤体质量明显降低(P<0.05),其中联合组较中药组和西药组的瘤体质量有明显降低(P<0.05)。p53和HIF-1的蛋白表达:与对照组相比,中药组、西药组和联合组的HIF-1的蛋白表达均明显下降(P<0.05);p53的蛋白表达明显上升(P<0.05)。联合组的HIF-1的蛋白表达较中药组和西药组有明显下降(P<0.05);p53的蛋白表达较中药组和西药组有明显升高(P<0.05)。PI3K、AKT、NF-KB基因表达:与对照组相比,中药组、西药组和联合组的PI3K、AKT和NF-KB基因表达均明显降低(P<0.05),联合组的趋势更加明显(P<0.05)。结论乳岩宁联合依西美坦可能通过抑制PI3K和AKT的表达来提高p53的活性,并同时限制HIF-1和NF-KB的表达,从而达到抑制肿瘤细胞的生长。

Objective To explore the regulatory mechanism on cancer inhibition of Chinese herbal compound Ruyanning combined exemestane on breast tumor bearing nude mice. Methods After the model of breast tumor bearing nude mice was established,the rats were divided into four groups including control group,Ruyanning group,exemestane group and combined（ Ruyanning and exemestane） group. The rats were delivered by gavage once a day for 21 days,and removed the tumors and weighted. The expression of p53 and HIF-1 protein in each group was determined by Western blotting. Real-time fluorescence quantitative RT-PCR was used to detect the expression of PI3 K,AKT and NF-KB genes. Results Tumor weight：compared with control group,Ruyanning group,exemestane group and the combined group of tumor weight are less than the control group（ P〈0. 05）. The combined group is the least among all the groups（ P〈0. 05）. p53 and HIF-1： compared with control group,Ruyanning group,exemestane group and the combined group of the expression of HIF-1 is less than the control group（ P〈0. 05）,while p53 is more than the control group（ P〈0. 05）. The combined group is more significant especially（ P〈0. 05）. PI3 K,AKT and NF-KB： compared with control group,Ruyanning group,exemestane group and the combined group of the expressions on PI3 K,AKT and NF-KB are less than the control group（ P〈0. 05）,and the combined group is more significant especially（ P〈0. 05）. Conclusions Ruyanning combined exemestane could control the activation of PI3 K and AKT genes to enhance the activity of p53,at the same time it could hold up the expression of HIF-1 and NF-KB,which would lead to restrain tumor cell proliferation.