文献类型：期刊文献

中文题名：归芪白术方联合奥沙利铂对胃癌荷瘤小鼠EGFR,VEGFR2表达和血管生成的影响

英文题名：Effect of Guiqi Baizhu Prescription Combined with Oxaliplatin on Expression of EGFR and VEGFR2 and Angiogenesis in Gastric Cancer-bearing Mice

作者：张晗[1,2];苏韫[1,2];龚红霞[1,2];黄勇[1,2];牛世伟[1,2];曾元丁[1,2]

第一作者：张晗

机构：[1]甘肃中医药大学基础医学院,兰州730000;[2]甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室,兰州730000

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2022

卷号：28

期号：7

起止页码：57

中文期刊名：中国实验方剂学杂志

外文期刊名：Chinese Journal of Experimental Traditional Medical Formulae

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金项目(81660744);甘肃省中医药研究中心专项(zyzx-2020-zx18);甘肃省高等学校创新基金项目(2020A-072);中西医结合基础学科科研培育项目(11)。

语种：中文

中文关键词：表皮生长因子受体(EGFR);血管内皮生长因子受体2(VEGFR2);胃癌;归芪白术方;血管生成

外文关键词：epidermal growth factor receptor(EGFR);vascular endothelial growth factor receptor-2(VEGFR2);gastric cancer;Guiqi Baizhu prescription;angiogenesis

摘要：目的:探讨归芪白术方联合奥沙利铂对胃癌荷瘤小鼠表皮生长因子受体(EGFR)、血管内皮生长因子受体2(VEGFR2)表达及血管生成的影响。方法:昆明种小鼠进行实验并建立胃癌荷瘤模型,造模成功后将小鼠随机分成6组:空白组、模型组、奥沙利铂组(10 mg·kg^(-1))、联合高、中、低剂量组(奥沙利铂10 mg·kg^(-1)联合归芪白术方17.68、8.84、4.42 g·kg^(-1));末次给药后,取移植瘤,计算抑瘤率;苏木素-伊红(HE)染色观察瘤组织形态学变化;酶联免疫吸附测定法(ELISA)检测血清表皮生长因子(EGF),白细胞介素-8(IL-8)、血管内皮生长因子(VEGF)水平;蛋白免疫印迹法(Western blot)和免疫组化法(IHC)检测EGFR、磷酸化EGFR(p-EGFR)、VEGFR2、磷酸化VEGFR2(p-VEGFR2)和血小板-内皮细胞黏附分子(CD31)的表达;实时荧光定量聚合酶链式反应(Real-time PCR)检测EGFR、VEGFR2 mRNA相对表达。结果:给药组瘤体质量较模型组显著下降(P<0.01);与奥沙利铂组比较,联合高、中剂量组瘤体质量明显下降(P<0.05,P<0.01);模型组肿瘤细胞密度较高,细胞形状规则,未见明确的组织坏死灶;给药组肿瘤细胞密度降低,可见明确的组织坏死灶及大规模炎性细胞;与空白组比较,模型组与给药组血清中EGF,VEGF和IL-8水平均明显上升(P<0.05,P<0.01);与模型组比较,给药组血清中EGF、VEGF和IL-8水平显著降低(P<0.01),EGFR、p-EGFR、VEGFR2、p-VEGFR2和CD31蛋白及EGFR、VEGFR mRNA表达显著降低(P<0.01);与奥沙利铂组比较,联合高、中剂量组EGF、VEGF和IL-8水平明显降低(P<0.05,P<0.01),EGFR、p-EGFR、VEGFR2、p-VEGFR2和CD31蛋白及EGFR、VEGFR2 mRNA表达明显下降(P<0.05,P<0.01);联合低剂量组中EGF、VEGF和IL-8含量降低,EGFR、p-EGFR、VEGFR2、p-VEGFR2和CD31蛋白及EGFR、VEGFR2 mRNA表达也有所下降,但差异无统计学意义。结论:归芪白术方联合奥沙利铂能通过影响EGFR,VEGFR2的表达,抑制胃癌荷瘤小鼠肿瘤组织的生长和血管生成。
Objective:To investigate the effect of Guiqi Baizhu prescription(GQBZ)combined with oxaliplatin on the expression of epidermal growth factor receptor(EGFR)and vascular endothelial growth factor receptor-2(VEGFR2)and angiogenesis in gastric cancer-bearing mice.Method:The tumor-bearing model of gastric cancer was induced in Kunming mice.The mice were randomly divided into blank group,model group,oxaliplatin group(10 mg·kg^(-1)),and high-(17.68 g·kg^(-1)),medium-(8.84 g·kg^(-1)),and low-dose(4.42 g·kg^(-1))combination groups(GQBZ combined with oxaliplatin).After the last administration,the transplanted tumor was collected and the tumor inhibition rate was calculated.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of tumor tissues.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum content of epidermal growth factor(EGF),interleukin-8(IL-8),and vascular endothelial growth factor(VEGF).Western blot and immunohistochemistry(IHC)were used to detect the expression of EGFR,phosphorylated EGFR(p-EGFR),VEGFR2,phosphorylated VEGFR2(p-VEGFR2),and platelet-endothelial cell adhesion molecule(CD31).Real-time fluorescence-based quantitative polymerase chain reaction(Real-time PCR)was used to detect the mRNA expression of EGFR and VEGFR2.Result:The tumor weight in the drug intervention groups was significantly lower than that in the model group(P<0.01).Compared with the oxaliplatin group,the high-and medium-dose combination groups showed reduced tumor weight(P<0.05,P<0.01).The tumor cells in the model groups were high in cell density and regular in shape,and no clear tissue necrosis was seen.The tumor cell density in the drug intervention groups was reduced,and clear tissue necrosis and large-scale inflammatory cells were visible.Compared with the blank group,the model group and the drug intervention groups showed increased serum levels of EGF,VEGF,and IL-8(P<0.05,P<0.01).Compared with the model group,the drug intervention groups showed decreased serum levels of EGF,VEGF,and IL-8(P<0.01),reduced protein expression of EGFR,p-EGFR,VEGFR2,p-VEGFR2,and CD31,and declining mRNA expression of EGFR and VEGFR(P<0.01).Compared with the oxaliplatin group,the high-and mediumdose combination groups showed decreased serum levels of EGF,VEGF,and IL-8(P<0.05,P<0.01),reduced protein expression of EGFR,p-EGFR,VEGFR2,p-VEGFR2,and CD31,and dwindled mRNA expression of EGFR and VEGFR2(P<0.05,P<0.01).The low-dose combination group showed decreased serum levels of EGF,VEGF,and IL-8,reduced protein expression of EGFR,p-EGFR,VEGFR2,p-VEGFR2,and CD31,and dwindled mRNA expression of EGFR and VEGFR2,but the difference was not statistically significant.Conclusion:GQBZ combined with oxaliplatin can inhibit the growth and angiogenesis of tumor tissues in gastric cancer-bearing mice by affecting the expression of EGFR and VEGFR2.