苏拉明联合紫杉醇对LA795肺腺癌小鼠移植瘤生长的抑制作用及机制

摘要

目的 观察苏拉明联合紫杉醇对LA795肺腺癌小鼠移植瘤生长的抑制作用,并探讨其作用机制.方法 将32只皮下接种LA795肺腺癌细胞T739小鼠随机分为对照组、紫杉醇组、苏拉明组和联合组,每组8只.观察移植瘤生长情况,饲养24 d后处死小鼠,剥离皮下移植瘤,采用免疫组化检测移植瘤组织中血管生成素-2(Ang-2)和微血管密度(MVD).结果 紫杉醇组、苏拉明组和联合组移植瘤的生长明显受到抑制,以联合组生长最慢.对照组移植瘤质量大于其他3组(P＜0.05).紫杉醇组和苏拉明组移植瘤质量大于联合组(P＜0.05);苏拉明组、紫杉醇组及联合组的抑瘤率分别为22.638%、25.629%及54.109%,其Q值为1.274(＞1.15).苏拉明组和联合组移植瘤组织内Ang-2的表达均低于对照组和紫杉醇组(P＜0.05).对照组移植瘤组织内MVD高于其他3组(P＜0.05);紫杉醇组或苏拉明组移植瘤组织内MVD高于联合组(P＜0.05).移植瘤组织中Ang-2表达、MVD与移植瘤质量均呈正相关(r=0.468、0.526,P＜0.01).结论 苏拉明可下调肿瘤组织Ang-2表达,抑制肿瘤内微血管形成,与紫杉醇联合对LA795肺腺癌小鼠皮下移植瘤生长发挥协同抑制作用.%Objective To observe the inhibitory effect of surarnin combined with paclitaxel on growth of transplanted LA795 lung adenocarcinoma in mice and explore its mechanism.Methods 32 T739 mice inoculated subcutaneously with LA795 lung adenocarcinoma cells were randomly divided into the control , paclitaxel , suramin and combination group, with 8 mice in each group.The growth of transplanted carcinoma were observed.Mice were sacrificed after 24 d feeding,and then the subcutaneous transplanted carcinoma were peeled.Angiopietin-2 ( Ang-2 ) and microvessel density( MVD) of transplanted carcinoma tissue were detected by immunohistochemistry.Results The growth of transplanted carcinoma in the paclitaxel, suranmin and combination group were suppressed significantly,and the lowest growth was found in the combination group.The mass of transplanted carcinoma in the control group was greater than those in the other 3 groups(P＜0.05) ,and those in the paclitaxel and suramin group were greater than that in the combination group(P＜0.05) ;Carcinoma inhibitory rates in the suramin, paclitaxel and combination group were 22.638％ ,25.629％ and 54.109％ , respectively , and the Q value was 1.274 (＞1.10).Ang-2 expression of transplanted carcinoma tissue in the suramin and combination group were both lower than those in the control and paclitaxel group(P＜0.05).MVD of transplanted carcinoma tissue in the control group was higher than those in the other 3 groups (P＜0.05) , and that in the paclitaxel group or suramin group was higher than in combination group (P＜0.05).Ang-2 expression or MVD in transplanted carcinoma tissue showed positive correlation with the carcinoma mass(r= 0.468 , 0.526 , P＜0.01 ).Conclusion Suramin may down-regulate Ang-2 expression in carcinoma tissue,inhibit the formation of microvessel in carcinoma and play a synergistic inhibitory role in growth of transplanted LA795 lung adenocarcinoma in mice with paclitaxel.