补肾健脾方对裸鼠原位肝癌切除术后复发瘤体血管生成拟态形成以及肺转移影响的研究  

Study on the effects of Bushen Jianpi Formula on vasculogenic mimicry of recurrence tumor and lung metastasis after hepatectomy in nude mice with carcinoma in situ

作　　者：付淑娟[1] 吴伟忠[2] 高东梅[2] 吴婷婷[1] 张士强[1] 杨蕴[1] 蒋海燕[1] 夏晓婷[1] 吕俊强[1] 周张杰 钟薏[1] 

机构地区：[1]上海中医药大学附属上海市中西医结合医院肿瘤科,上海200082 [2]复旦大学附属中山医院肝癌研究所,上海200032

出　　处：《北京中医药》2017年第5期425-428,F0003,共5页Beijing Journal of Traditional Chinese Medicine

基　　金：上海市卫生局中医药科研基金资助项目(2012J003A)

摘　　要：目的观察补肾健脾方对人肝癌高转移原位移植瘤裸鼠切除术后血管生成拟态(Vasculogenic Mimicry,VM)形成以及肺转移的影响。方法建立HCCLM3原位荷瘤切除术后复发转移裸鼠模型,分为补肾健脾方组(A组)、索拉非尼组(B组)、联合用药组(C组)、模型对照组(D组),每组7只。术后第3天起,给予相应药物灌胃,共给药28天,每天1次。末次给药后48 h处死裸鼠并取材,采用免疫组化法检测复发瘤体VE-cadherin、Eph A2、PI3K、FAK蛋白表达,计算血管生成拟态密度(Vasculogenic mimicry density,VMD)以及肺转移细胞数。结果 (1)VMD:C组与其余3组比较,VECadherin蛋白阳性面积显著降低(P<0.05)。与D组相比较,A和C组Eph A2蛋白表达显著降低(P<0.05);A、B、C组PI3K、FAK蛋白表达均显著下调(P<0.05)。VMD由低到高依次为C、A、B、D组,与D组比较,下调倍数依次为1.4、1.2、1.1倍,但差异无统计学意义(P>0.05)。(2)肺转移细胞数:与D组比较,A、C组肺转移肿瘤细胞数显著减少(P<0.05)。结论补肾健脾方能有效降低VE-Cadherin、Eph A2、PI3K、FAK蛋白的表达,减少肺部转移;与索拉非尼联用时,对VE-Cadherin、Eph A2蛋白表达抑制尤为显著,能最大程度阻止VM的形成,降低肺部转移。Objective To observe the effects of Bushen Jianpi Formula on vasculogenic mimicry （ VM ） and lung metastasis in high metastasis nude mice with human hepatoeellular carcinoma （ HCC ） after hepatectomy. Methods Nude mice model with postoperative recurrence of metastasis after hepatectomy in human hepatocellular carcinoma （ HCCLM3 ） in situ were established. They were divided into the group of Bushen Jianpi Formula group（ Group A） , Sorafenib group（ group B） , combined medicine group（ group C）and model control group（group D） , 7 in each group. From the 3rd day after hepatectomy, they all received gavage once a day for 28 days with corresponding drugs. 48 hours after the last treatment, they were executed to get sample. The expression of VE-cadherin, EphA2, PI3K, FAK of recurrence tumor were detected by immunohistochemistry, vasculogenic mimicry density （VMD）and lung metastasis tumor cells were calculated. Results 1. VMD ： compared with other 3 groups, VE-Cadherin expressed less in Group C （ P 〈 0.05 ）. EphA2 protein expression was lower in Group A and C than D（P 〈0. 05）. The expression of PI3K and FAK of Group A, B and C were lowered（P 〈 0.05）. VMD ranked from low to high as follows： Group C, A, B, D, the lowering times were 1.4, 1.2, 1.1 respectively compared with group D, while there was no statistical difference （ P 〉 0. 05 ）. 2. Lung metastasis cell numbers ： Group A and C had less lung metastasis tumor cells than Group D （ P 〈 0. 05 ）. Conclusion Bushen Jianpi Formula could effectively inhibit protein expression of VE-Cadherin, EphA2, PI3K and FAK and decrease lung metastasis. When both Bushen Jianpi formula and Sorafenib are given, the inhibition effect on VE-Cadherin and EphA2 protein expression is more remarkable as VM could be stopped and lung metastasis reduced to the maximum extent.

关 键 词：补肾健脾方 肝癌 术后复发 肺转移 血管生成拟态 裸鼠 

分 类 号：R285.5[医药卫生—中药学]