消岩汤联合甲磺酸阿帕替尼对胃癌荷瘤小鼠移植瘤的抑瘤作用及机制研究

Inhibitory effect and mechanism of Xiaoyan Decoction combined with Apatinib Mesylate on transplanted tumor of gastric cancer bearing mice

关键词:  消岩汤  阿帕替尼  胃癌  PI3K/AKT 信号通路  血管新生

Key words:  Xiaoyan Decoction  Apatinib  gastric cancer  PI3K/AKT signal pathway  angiogenesis

摘要:

[目的] 探讨消岩汤联合甲磺酸阿帕替尼对胃癌荷瘤小鼠移植瘤的抑瘤作用及抗肿瘤作用机制。[方法] 将胃癌MFC细胞接种于BALB/c雄性小鼠皮下，成瘤后随机分为荷瘤模型组、消岩汤组、阿帕替尼组以及联合用药组，未造模的为空白对照组，每组5只。各组小鼠分别灌胃予生理盐水以及相应药物，连续给药14 d，观察记录小鼠生活状况及肿瘤体积变化。给药结束后处死各组小鼠，取肿瘤组织，称量质量记录，并利用蛋白免疫印迹（Western Blot）法检测瘤组织中磷脂酰肌醇3-激酶（PI3K）/丝苏氨酸蛋白激酶（AKT）信号通路及血管新生相关蛋白的表达。[结果] 观察各组小鼠的生活状况显示，消岩汤组和阿帕替尼组小鼠的生活状况较荷瘤模型组有所改善，联合用药组小鼠改善更为明显；与荷瘤模型组比较，消岩汤组、阿帕替尼组以及联合用药组的肿瘤体积及质量明显降低，联合用药组降低更为明显；相较于荷瘤模型组，消岩汤组、阿帕替尼组以及联合用药组的p-PI3K、p-AKT、Bcl-2、基质金属蛋白酶（MMP）-9、MMP-2、血管内皮生长因子A（VEGFA）和血管内皮生长因子受体-2（VEGFR-2）的蛋白表达明显下调，Cleaved Caspase-9、Bax的蛋白表达明显上调，差异均具有统计学意义（P<0.05），与单药组比较，联合用药组对PI3K/AKT信号通路及血管新生相关蛋白表达的调控作用更为明显。[结论] 消岩汤联合阿帕替尼可通过调控PI3K/AKT信号通路和血管新生相关蛋白的表达，有效抑制胃癌小鼠移植瘤的生长，改善小鼠生活状况。

Abstract:

[Objective] To investigate the antitumor effect and antitumor mechanism of Xiaoyan Decoction combined with Apatinib Mesylate on transplanted tumor of gastric cancer bearing mice. [Methods] Gastric cancer MFC cells were inoculated subcutaneously into BALB/C male mice. After tumor formation， they were randomly divided into model group， Xiaoyan Decoction group， Apatinib group and combined drug group. The non model group was blank control group， with 5 rats in each group. Mice in each group were given normal saline and corresponding drugs by gavage for 14 days. The living conditions and tumor volume changes of mice were observed and recorded. After administration， mice in each group were killed， tumor tissues were taken， weighed and recorded， and the expression of PI3-K/Akt signal pathway and angiogenesis related protein in tumor tissues were detected by Western blot. [Results] The observation of the living conditions of mice in each group showed that the living conditions of mice in Xiaoyan Decoction group and Apatinib group were better than those in model group， and the improvement of mice in combined drug group was more obvious；compared with the tumor bearing model group， the tumor volume and mass of Xiaoyan Decoction group， Apatinib group and combined drug group were significantly reduced， especially in the combined drug group；compared with the tumor bearing model group， the protein expressions of p-PI3K， p-AKT， Bcl-2， MMP-9， MMP-2， VEGFA and VEGFR-2 in Xiaoyan Decoction group， Apatinib group and combined drug group were significantly down regulated， and the protein expressions of Cleaved Caspase-9 and Bax were significantly up-regulated（P<0.05）.Compared with the single drug group， the combined drug group had more obvious regulatory effect on PI3K/Akt signal pathway and angiogenesis related protein expression. [Conclusion] Xiaoyan Decoction combined with Apatinib can effectively inhibit the growth of transplanted tumor in gastric cancer mice and improve the living conditions of mice by regulating the expression of PI3K/Akt signal pathway and angiogenesis related protein.