扶正散结汤拆方对Lewis肺癌移植瘤MVD、HIF-1α及COX-2的影响

Effects of Fuzheng Sanjie Recipe on tumor MVD,HIF- 1α and COX- 2 in Mice with Lewis Transplantation Lung Cancer

目的观察扶正散结汤拆方对Lewis肺癌小鼠移植瘤微血管密度的影响及其在缺氧诱导微血管生成通路的作用机制。方法 C57BL/6小鼠80只,随机分成空白组、模型组、顺铂组(DDP组)、益气扶正组(扶正组)、化痰散结组(化痰组)、活血化瘀组(活血组)、清热解毒组(解毒组)和联合用药组,每组10只,除空白组外其余各组建立Lewis肺癌移植瘤模型后,分别给予相应药物干预,连续14 d,于第15天处死后剥离肿瘤组织,免疫组化SP法检测肿瘤组织中CD34、肿瘤组织中缺氧诱导因子1α(HIF-1α)、环氧化酶2(COX-2)表达。结果各用药组均能明显降低瘤组织MVD,以联用组最接近DDP组,其次为扶正组和活血组;与模型组比较,顺铂组及各中药组HIF-1α表达均降低(P<0.05,P<0.01),其中联用组、顺铂组及扶正组降低较明显。与模型组比较,各用药组COX-2表达量均呈下降趋势,以解毒组与联用组最低(P<0.01),其次为活血组和化痰组,而DDP组与扶正组最接近于模型组,差异无统计学意义。结论扶正散结汤各拆方组分能抑制肿瘤血管新生,各抗癌组分在肿瘤缺氧通路及之外的其他通路上抑制肿瘤血管生成具有不同的作用特点和机制,而联合应用则可最大程度发挥抑制血管生成的作用。

Objective To observe the mechanism of Fuzheng Sanjie Recipe on Lewis lung cancer mice transplanted tumor microvessel density and hypoxia induced angiogenesis pathway. Methods Eighty C57BL/6 mice were randomly divided into Blank group, Model group, DDP group, Yiqifuzheng group, Hua- tansanjie group, Huoxuehuayu group, Qingrejiedu group and Combination group. In addition to the blank group, other groups to establish Lewis lung cancer xenograft model, and received drugs intervention for 14 days. On Day Fifteen,tumor tissue were stripped after animal was killed. Detected the expression of CD34, HIF - 1α, COX - 2 by streptavidin - perosidase immunohistochemical method in tumor tissue. Results The treatment groups significantly reduced the tumor microvessel density, combination group close to the DDP group, followed by Fuzheng group and Huoxue group. Compared with the model group,the expression of HIF - 1α in DDP group and TCM groups decreased（P 〈0.05 ,P 〈0.01 ）. DDP group,Combination group and Fuzheng group decreased significantly（ there were no significant difference among the three groups） ,being followed by Huoxue group, Jiedu group and Huatan group where no difference as compared with prior the study was observed. The expression of COX - 2 decreased in all the other groups decreased, when compared with the model group, with Jiedu group and Combination group being the lowest （P 〈 0.01 ）, followed by Huoxue group and Huatan group, DDP group and Fuzheng group close to the model group. Conclusion Fuzheng Sanjie Recipe groups can inhibit tumor angiogenesis, the anticancer components in tumor hypoxia pathway and other pathways on the inhibition of tumor angiogenesis with different characteristics and mechanisms, and the combined application can maximize the effects of inhibiting angiogenesis.