文章摘要
任宝恒,丁海斌,杨栓盈,范志刚,陈 旭,陈 静.miR-10a通过FBXW7-ZEB2轴调控非小细胞肺癌肿瘤化疗耐药的动物实验研究[J].,2022,(13):2431-2435
miR-10a通过FBXW7-ZEB2轴调控非小细胞肺癌肿瘤化疗耐药的动物实验研究
The Animal Experiment Study of miR-10a Regulating the Chemotherapy Resistance of Non-small Cell Lung Cancer through the FBXW7-ZEB2 Axis
投稿时间:2021-12-06  修订日期:2021-12-31
DOI:10.13241/j.cnki.pmb.2022.13.006
中文关键词: MiR-10a  非小细胞肺癌  小鼠  含F-框WD重复域蛋白7  E盒锌指结合蛋白2  化疗耐药  细胞凋亡
英文关键词: MiR-10a  Non-small cell lung cancer  Mice  F-box WD repeat domain protein 7  E-box zinc finger binding protein 2  Chemotherapy resistance  Apoptosis
基金项目:陕西省重点研发计划项目(2021SF-044)
作者单位E-mail
任宝恒 西安交通大学医学院附属三二〇一医院呼吸与危重症医学科 陕西 汉中 723000 renbaoheng1972@126.com 
丁海斌 陕西省肿瘤医院内二科 陕西 西安 710061  
杨栓盈 西安交通大学第二附属医院呼吸与危重症医学科 陕西 西安 710006  
范志刚 西安交通大学医学院附属三二〇一医院肿瘤内一科 陕西 汉中 723000  
陈 旭 陕西省肿瘤医院内二科 陕西 西安 710061  
陈 静 陕西省肿瘤医院内二科 陕西 西安 710061  
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中文摘要:
      摘要 目的:通过动物实验,具体探讨微小RNA(miR-10a)通过含F-框WD重复域蛋白7(FBXW7)-E盒锌指结合蛋白2(ZEB2)轴调控非小细胞肺癌的肿瘤化疗耐药作用。方法:非小细胞肺癌模型小鼠(n=42)随机平分为三组-模型组、miR-10a组与环磷酰胺组,模型组给予生理盐水0.2 mL腹腔注射,环磷酰胺组给予环磷酰胺20 mg/kg腹腔注射,miR-10a组给hsa-miR-10a mimics 15 mg/kg 联合环磷酰胺20 mg/kg腹腔注射,1次/d,持续给药14 d。结果:miR-10a组与环磷酰胺组治疗第7 d与第14 d的肿瘤体积低于模型组,miR-10a组低于环磷酰胺组(P<0.05)。miR-10a组与环磷酰胺组治疗第14 d与第28 d的瘤体质量低于模型组,抑瘤率高于模型组,miR-10a组与环磷酰胺组对比差异也有统计学意义(P<0.05)。miR-10a组与环磷酰胺组治疗第14 d与第28 d的肿瘤细胞凋亡指数高于模型组,miR-10a组高于环磷酰胺组(P<0.05)。miR-10a组与环磷酰胺组治疗第14 d与第28 d的血清FBXW7、ZEB2含量低于模型组,miR-10a组低于环磷酰胺组(P<0.05)。miR-10a组与环磷酰胺组治疗第14 d与第28 d的FBXW7、ZEB2 mRNA与蛋白相对表达水平低于模型组,miR-10a组低于环磷酰胺组(P<0.05)。结论:过表达miR-10a能抑制非小细胞肺癌小鼠的FBXW7-ZEB2轴的激活,抑制血清FBXW7、ZEB2的表达,从而促进肿瘤细胞凋亡,改善肿瘤化疗耐药性,促进缩小肿瘤体积。
英文摘要:
      ABSTRACT Objective: Through animal experiments, To specifically explore the passage of microRNA (miRNA, miR)-10a through F-Box and WD40 domain protein 7(FBXW7) and E-box zinc finger binding protein 2(ZEB2) axis regulates the tumor chemotherapy resistance of non-small cell lung cancer hrough animal experiments. Methods: Non-small cell lung cancer model mice (n=42) were randomly equally divided into three groups-model group, miR-10a group and cyclophosphamide group. The model group were given intraperitoneal injection of normal saline 0.2 mL, and the cyclophosphamide group were given cyclophosphamide 20 mg/kg intraperitoneally at 20 mg/kg, the miR-10a group were given hsa-miR-10a mimics 15 mg/kg combined with cyclophosphamide 20 mg/kg intraperitoneally, once daily for 14 d. Results: The tumor volume of the miR-10a group and the cyclophosphamide group were lower on the 7th and 14th day of treatment than the model group, and the miR-10a group were lower than that of the cyclophosphamide group (P<0.05). The tumor mass of miR-10a group and cyclophosphamide group on the 14th and 28th day of treatment were lower than that of the model group, and the tumor inhibition rate were higher than that of the model group, the difference compared between the miR-10a group and cyclophosphamide group were also statistically significant(P<0.05). The apoptosis index of tumor cells in the miR-10a group and the cyclophosphamide group were higher on the 14th and 28th day of treatment than the model group, and the miR-10a group were higher than the cyclophosphamide group(P<0.05). The levels of serum FBXW7 and ZEB2 in the miR-10a group and the cyclophosphamide group were lower on the 14th and 28th day of treatment than the model group, and the miR-10a group were lower than the cyclophosphamide group(P<0.05). The relative expression levels of FBXW7 and ZEB2 mRNA and protein in the miR-10a group and the cyclophosphamide group were lower than the model group on the 14th and 28th day of treatment, and the miR-10a group were lower than the cyclophosphamide group(P<0.05). Conclusion: Overexpression of miR-10a can inhibit the activation of FBXW7-ZEB2 axis in mice with non-small cell lung cancer, and inhibit the expression of serum FBXW7 and ZEB2, thereby promoting tumor cell apoptosis, improving tumor chemotherapy resistance, and promoting tumor volume reduction.
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