吴茱萸碱对结直肠癌小鼠IL-6R/STAT3通路的影响  

Inhibitory effect of evodiamine on colorectal cancer in mice and its effect on IL-6R/STAT3 pathway

作　　者：张超[1] 荣爱梅[1] 张磊[1] 王丹[1] ZHANG Chao;RONG Aimei;ZHANG Lei;WANG Dan(Department of Gastroenterology,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学附属郑州市中心医院消化内科,郑州450000

出　　处：《西北药学杂志》2022年第1期58-64,共7页Northwest Pharmaceutical Journal

摘　　要：目的探讨吴茱萸碱对结直肠癌小鼠的抑瘤作用及对白介素-6受体(interleukin-6 receptor,IL-6R)/信号转导转录激活因子3(signal transducer and activator of transcription 3,STAT3)通路的影响。方法将59只BALA/C小鼠随机留取9只作为对照组,其余皮下接种CT-26结直肠癌细胞株建立结直肠癌小鼠模型,将建模成功的40只小鼠随机分为模型组、顺铂组、吴茱萸碱组和顺铂+吴茱萸碱组,每组10只。顺铂组用15 mg·kg^(-1)·d^(-1)顺铂灌胃,顺铂+吴茱萸碱组用15 mg·kg^(-1)·d^(-1)顺铂+15 mg·kg^(-1)·d^(-1)吴茱萸碱灌胃,对照组、模型组用等量生理盐水灌胃。各组均每日灌胃1次,连续19周。末次灌胃24 h后,处死小鼠,称肿瘤质量并计算肿瘤体积、肿瘤抑制率;用酶联免疫吸附实验(enzyme linked immunosorbent assay,ELISA)检测小鼠肿瘤组织的白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;用HE染色观察小鼠肿瘤组织的病理学变化;用免疫组织化学法检测肿瘤组织的微血管密度(microvesse density,MVD)和血管内皮生长因子(vascular endothelial growth factor,VEGF)水平;用Western blot检测肿瘤组织中IL-6R/STAT3通路相关蛋白的表达水平。结果从模型组到吴茱萸碱组、顺铂组、顺铂+吴茱萸碱组,小鼠肿瘤的质量依次减轻、肿瘤体积依次减小,IL-6、IL-1β、TNF-α水平依次降低(P<0.05)。模型组小鼠肿瘤组织中可见大片灶性坏死,细胞核增大、深染,大小不一,排列紊乱,有异形表现,呈典型恶性肿瘤细胞形态特征,肿瘤细胞密集;吴茱萸碱组、顺铂组和顺铂+吴茱萸碱组的肿瘤细胞核固缩、变小,肿瘤细胞形态破坏,密度依次降低,肿瘤组织内坏死区依次增大,MVD依次减小(P<0.05),VEGF阳性表达依次减弱(P<0.05)。从模型组到吴茱萸碱组、顺铂组、顺铂+吴茱萸碱组,小鼠肿瘤组织中IL-6R、p-STAT3、G 1/S-特�Objective To investigate the effect of evodiamine on colorectal cancer in mice and the effect on interleukin-6 receptor(IL-6R)/signal transducer and actirator of transcription 3(STAT3)pathway.Methods 9 mice from total of 59 BALA/C mice were randomly selected as control group,and the rest were subcutaneously inoculated with CT-26 colorectal cancer cell line to establish colorectal cancer mouse model.40 model mice were randomly divided into model group,cisplatin group,evodiamine group and cisplatin+evodiamine group with 10 mice in each group.The cisplatin group were given 15 mg·kg^(-1)·d^(-1) cisplatin by gavage.In the cisplatin+evodiamine group,15 mg·kg^(-1)·d^(-1) cisplatin+15 mg·kg^(-1)·d^(-1) evodiamine were given by gavage.The control group and model group were given the same amount of normal saline.Each group were given gavage once a day for 19 weeks.24 hours after the last gavage,the mice were sacrificed,and the tumor volume and tumor inhibition rate were calculated.The levels of interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by enzyme linked immunosorbent assay(ELISA).The pathological changes of tumor tissue were observed by HE staining.The microvessel density(MVD)and vascular endothelial growth factor(VEGF)were detected by immunohistochemistry.The IL-6R/STAT3 pathway related proteins in tumor tissues were detected by Western blot.Results The tumor weight and volume,and the levels of IL-6,IL-1βand TNF-αof the model group,evodiamine group,cisplatin group,cisplatin+evodiamine group decreased in turn(P<0.05).In the model group,a large area of focal necrosis was found in the tumor tissue.The nuclei were enlarged and deeply stained,the size was different,and the arrangement was disordered.There were heteromorphic manifestations,and typical morphological characteristics of malignant tumor cells were observed.In evodiamine group,cisplatin group and cisplatin+evodiamine group,the nuclei of tumor cells were pyknosis and smaller,the morphology of tumor cells was d

关 键 词：吴茱萸碱 结直肠癌 人白介素-6受体/信号传导转录激活因子3通路 肿瘤抑制率 

分 类 号：R285.5[医药卫生—中药学]