摘要
目的研究植酸(IP6)与肌醇(INS)辅助卡培他滨对结直肠癌BALB/c小鼠的干预作用及其机制。方法在BALB/c雄性小鼠盲肠壁浆膜层下注射CT-26细胞建立小鼠结直肠癌原位移植模型,将造模成功的48只小鼠按IP6+INS(干预和不干预)和卡培他滨(干预和不干预)两个因素及两个因素的不同水平交叉组合分为4组,分别为模型组(A组)、卡培他滨组(B组)、IP6+INS组(C组)、卡培他滨+IP6+INS组(D组),每组12只,4组小鼠分别用生理盐水0.2 mL、60 mg/kg卡培他滨0.2 mL、80 mg/kg IP6和80 mg/kg INS共0.2 mL、60 mg/kg卡培他滨和80 mg/kg IP6及80 mg/kg INS共0.2 mL灌胃。眼球取血处死小鼠后,取原位瘤组织称质量,采用酶联免疫吸附测定法检测各组小鼠血清中趋化因子CCL20、白细胞介素10(IL-10)、白细胞介素12(IL-12)的水平。采用Western blot和RT-PCR方法检测小鼠原位瘤组织中基质金属蛋白酶2(MMP-2)和MMP-9蛋白及mRNA的表达。结果IP6+INS两者与卡培他滨合用对原位瘤质量,CCL20、IL-10、IL-12水平,MMP-2蛋白及mRNA,MMP-9蛋白及mRNA有交互作用(F=5.731~50.311,P<0.05),当有或无卡培他滨干预时,IP6+INS对原位瘤质量,CCL20、IL-10、IL-12水平,MMP-2蛋白及mRNA,MMP-9蛋白及mRNA水平均有明显影响(F=7.330~321.372,P<0.05),当有或无IP6+INS干预时,卡培他滨对原位瘤质量,CCL20、IL-10、IL-12水平,MMP-2蛋白及mRNA表达,MMP-9蛋白及mRNA表达均有明显影响(F=10.687~757.673,P<0.05)。结论IP6+INS辅助卡培他滨可以抑制BALB/c小鼠结直肠癌的生长,其作用机制可能与影响炎症因子以及MMP-2、MMP-9 mRNA以及蛋白的表达有关。
Objective To investigate the intervention effect and mechanism of phytic acid(IP6)and inositol(INS)combined with capecitabine on BALB/c mice with colorectal cancer.Methods Male BALB/c mice were given the injection of CT-26 cells into the serosa of the cecal wall to establish an orthotopic transplantation model of colorectal cancer,and according to the two factors of IP6+INS(intervention and non-intervention)and capecitabine(intervention and non-intervention)and the different le-vels of cross combination of the two factors,48 mice after successful modeling were divided into model group(group A),capeci-tabine group(group B),IP6+INS group(group C),and capecitabine+IP6+INS group(group D),with 12 mice in each group.The mice in group A were given 0.2 mL normal saline,those in group B were given 0.2 mL of 60 mg/kg capecitabine,those in group C were given 0.2 mL of 80 mg/kg IP6 and 80 mg/kg INS,and those in group D were given 0.2 mL of 60 mg/kg capeci-tabine,80 mg/kg IP6,and 80 mg/kg INS,all by gavage.After the mice were sacrificed and blood samples were collected from the eyeballs,orthorotopic transplanation tumor tissue was weighed,and ELISA was used to measure the serum level of the chemokine C-C motif chemokine ligand 20(CCL20),interleukin-10(IL-10),and interleukin-12(IL-12).Western blot and RT-PCR were used to measure the protein and mRNA expression of matrix metalloproteinase-2(MMP-2)and MMP-9 in orthotopic transplantation tumor tissue.Results IP6 and INS combined with capecitabine has an interactive effect on the mass of orthotopic transplantation tumor,the serum levels of CCL20,IL-10,and IL-12,and the protein and mRNA expression of MMP-2 and MMP-9(F=5.731-50.311,P<0.05).With or without capecitabine intervention,IP6+INS had a significant effect on the mass of orthotopic transplantation tumor,the serum levels of CCL20,IL-10,and IL-12,and the protein and mRNA expression of MMP-2 and MMP-9(F=7.330-321.372,P<0.05).With or without IP6+INS intervention,capecitabine also had a significant effect on the mass of orthotopic transplantation tumor,the serum levels of CCL20,IL-10,and IL-12,and the protein and mRNA expression of MMP-2 and MMP-9(F=10.687-757.673,P<0.05).Conclusion IP6 and INS can assist capecitabine in inhibiting the growth of colorectal tumor in BALB/c mice,possibly by affecting the expression of inflammatory factors and the protein and mRNA expression of MMP-2 and MMP-9.
作者
慈一帆
王海桃
刘晓涵
陈沉
李倩倩
宋扬
CI Yifan;WANG Haitao;LIU Xiaohan;CHEN Chen;LI Qianqian;SONG Yang(School of Public Health, Qingdao University, Qingdao 266071, China)
出处
《精准医学杂志》
2020年第4期313-317,共5页
Journal of Precision Medicine
基金
国家自然科学基金资助项目(81973033)。
