华蟾素注射液抗结肠癌移植瘤血管新生的作用研究

Anti-tumor-angiogenesis effect of Cinobufagin Injection on colon cancer transplantation model

目的探讨华蟾素注射液对结肠癌移植瘤血管新生的影响。方法皮下注射CT26细胞,建立结肠癌移植瘤模型。造模成功后采用随机数字表法将20只荷瘤小鼠随机分成五组,即华蟾素注射液高剂量组(CINO-H组)、华蟾素注射液中剂量组(CINO-M组)、华蟾素注射液低剂量组(CINO-L组)、5-氟尿嘧啶(5-FU)组及生理盐水组,每组4只。CINO-H组给予华蟾素注射液0.5 m L,CINO-M组给予华蟾素注射液0.25 m L+生理盐水0.25 m L,CINO-L组给予华蟾素注射液0.125 m L+生理盐水0.375 m L,5-FU组给予5-FU注射液(20 mg/kg),用生理盐水配制成0.5 m L,生理盐水组给予生理盐水0.5 m L。每天腹腔内注射给药1次,连续给药7 d。观察小鼠一般状态、移植瘤大小、组织病理学及微血管密度(MVD)。结果 5-FU组瘤体积明显小于生理盐水组,差异有统计学意义(P<0.05),但华蟾素注射液各剂量组与生理盐水组比较差异无统计学意义(P>0.05)。从组织病理学观察可得,华蟾素注射液可使瘤体呈现不同程度的坏死,但坏死程度不如5-FU。华蟾素注射液各剂量组MVD均较生理盐水组明显降低,差异有高度统计学意义(P<0.01),而5-FU组MVD与生理盐水组比较差异无统计学意义(P>0.05)。结论华蟾素注射液能抑制肿瘤组织血管新生,减少瘤体内MVD,抑制肿瘤的生长。

Objective To invesLigaLe anLi-Lumor-angiogenesis effecL of Cinobufagin InjecLion on colon cancer Lrans-planLaLion model.Methods Mice were administered wiLh CT26 cells by subcuLaneous injecLion Lo esLablish colon cancer LransplanLaLion model.Then,modeled mice were divided randomly inLo 5 groups:high dose of Cinobufagin InjecLion group(CINO-H group),medium dose of Cinobufagin InjecLion group(CINO-M group),low dose of Cinobufagin Injec-Lion group(CINO-L group),5-Fluorouracil(5-FU)group and normal saline group,wiLh 4 mice in each group.CINO-H group was given Cinobufagin InjecLion 0.5 mL,CINO-M group was given Cinobufagin InjecLion 0.25 mL+normal saline 0.25 mL,CINO-L group was given Cinobufagin InjecLion 0.125 mL+normal saline 0.375 mL,5-FU group was given 5-FU InjecLion 20 mg/kg,allocaLed Lo 0.5 mL wiLh normal saline,normal saline group was given normal saline 0.5 mL.The mice were injecLed inLraperiLoneally wiLh drugs once a day,for 7 days.Tumor formaLion condiLions were observed,and paLhological examinaLion of LransplanLed Lumor and Lumor microvascular densiLy(MVD)was measured.Results The Lumor volume of 5-FU group was lower Lhan LhaL of normal saline group(P<0.05),buL Lhere was no sLa-LisLically significanL difference in Lumor volume beLween all Cinobufagin InjecLion groups and normal saline group(P>0.05).HisLopaLhological observaLion showed LhaL Cinobufagin InjecLion caused Lhe Lumor necrosis in differenL degrees,which was inferior Lo 5-FU.All Cinobufagin InjecLion groups decreased MVD in Lumor,and significanL differ-ence was shown in comparison wiLh Lhose in normal saline group(P<0.01).While,5-FU group couldn'L decrease MVD in Lumor(P>0.05).Conclusion Cinob-ufagin InjecLion can decrease MVD in Lumor by inhibiL-ing Lumor-angiogenesis,Lhus inhibiLing Lumor growLh.