乳岩宁联合依西美坦调控荷瘤裸鼠能量代谢的机制

The mechanism on energy metabolism of Chinese herbal compound Ruyanning combined with Exemestane on breast tumor bearing nude mice

目的探究乳岩宁联合依西美坦通过PI3k-AKT通路对乳腺癌荷瘤裸鼠能量代谢的调控机制。方法建立乳腺癌(MDA-MB-435)荷瘤裸鼠模型后,分为空白对照组、乳岩宁组、依西美坦组、联合组(依西美坦+乳岩宁组),每天灌胃给药1次,持续21 d。取材,称取各组瘤体质量。采用Western blotting法测定各组PI3k-AKT蛋白的表达。采用实时荧光定量RT-PCR法检测各组m TOR、HIF-1、LDH-A、GLUT1基因表达。结果瘤质量: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重有明显降低(P<0.05)。PI3k、AKT的蛋白表达:与对照组相比,中药组、西药组和联合组的PI3k、AKT的蛋白表达均明显下降(P<0.05)。联合组的PI3k和AKT的蛋白表达较中药组和西药组有明显下降(P<0.05)。m TOR、LDH、HIF和GLUT1基因表达:与对照组相比,中药组、西药组和联合组的m TOR、LDH、HIF和GLUT1基因表达均明显降低(P<0.05)。联合组的各项基因表达较中药组和西药组有明显下降(P<0.05)。结论乳岩宁联合依西美坦可能通过阻碍PI3k-AKT通路的激活,抑制下游基因m TOR、HIF-1、LDH-A和GLUT1的表达,以控制肿瘤细胞内糖酵解、蛋白质的合成以及新血管的形成等能量代谢活动,从而达到抑制肿瘤细胞生长的目的。

Objective To explore the mechanism on energy metabolism of Chinese herbal compound Ruyanning combined with Exemestane on breast tumor bearing nude mice though PI3k-AKT Signaling Pathway. Methods After breast tumor bearing nude mice model was established, the rats were divided into four groups including the control group ,Ruyanning group ,Exemestane group and combined（ Ruyanning and Exemestane ）group. The rats were delivered by garage once a day for 21 days, and the tumors were removed and weighted. The expressions of PI3k and AKT protein were detected by Western Blotting, and the expressions of mTOR, HIF-1, LDH-A and GLUT1 were detected by real-time quantitative RT-PCR. Results Tumor weight：Compared with control group, the tumor weight of Ruyanning group, Exemestane group and the combined group were less than the control group （ P 〈 0. 05 ）. The tumor weight of combined group was the lightest among all （ P 〈 0. 05 ）. PI3k and AKT： Compared with control group, the expression of PI3k- AKT of Ruyanning group, Exemestane group and the combined group was less than the control group （P 〈 0. 05 ）. And the combined group was the least among all the groups （P 〈 0. 05 ）. The expression of mTOR, LDH, HIF and GLUT1 ： Compared with control group, Ruyanning group, Exemestane group and combined group had less expression on mTOR,LDH, HIF and GLUT1 compared with control group（ P 〈 0. 05 ）. And the combined group had the least expression among all （ P 〈 0. 05 ）. Conclusions Ruyanning combined Exemestane could control the activation of PI3k-AKT pathway to hold up the expression of its downstream gene such as mTOR, LDH, HIF and GLUT1. These will restrain energy metabolism like glycolysis, protein synthesis and the development of new blood vessels inside tumor cells,inhibiting the tumor cell proliferation.