放疗通过缺乏氧诱导因子-1α及表皮因子生长受体相关通路抑制路易斯肺癌小鼠的肿瘤发展  

Radiotherapy inhibits tumor development in mice with Lewis lung cancer through hypoxiainducible factor-1αand epidermal growth factor receptor pathways

作　　者：陈飞[1] 李佳[1] 张鹏飞[2] 李智宇[3] Chen Fei;Li Jia;Zhang Pengfei;Li Zhiyu(Department of Radiotherapy,Shanxi Provincial Cancer Hospital,Chinese Academy of Medical Sciences Cancer Hospital,Shanxi Hospital,Shanxi Medical University,Taiyuan 030013,China;The Department of Neurosurgery of the General Hospital of the Chinese People's Liberation Army stationed in the Seventh Medical Center Neurosurgery,Beijing 100000,China;Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences,Beijing 100021,China)

机构地区：[1]山西省肿瘤医院、中国医学科学院肿瘤医院山西医院、山西医科大学附属肿瘤医院放射治疗科,太原030013 [2]中国人民解放军总医院神经外科学部派驻第七医学中心神经外科,北京100000 [3]中国医学科学院肿瘤医院肝胆外科,北京100021

出　　处：《中华实验外科杂志》2024年第10期2256-2259,共4页Chinese Journal of Experimental Surgery

基　　金：国家卫生健康委项目(2018MND102006);吴阶平医学基金会临床科研专项(320.6750.2021-23-6)。

摘　　要：目的:建立路易斯(Lewis)肺癌小鼠模型,并探究放疗对肿瘤的抑制效果以及对表皮因子生长受体/磷脂酰肌醇3激酶/丝氨酸-苏氨酸激酶(EGFR/PI3K/Akt)及缺乏氧诱导因子-1α/血管内皮生长因子(HIF-1α/VEGF)信号通路表达的影响。方法:共计24只无特定病原体级别的C57BL/6小鼠,通过腋下接种Lewis肺癌细胞构建Lewis肺癌小鼠模型,通过随机数字表法将小鼠分为对照组和实验组,每组12只。对照组不进行放疗,实验组在接种后第14天开始进行6MV-X射线放疗。放疗结束后处死,解剖,计算抑瘤率,苏木精-伊红(HE)染色观察组织病理,原位末端标记法(TUNEL)染色观察细胞凋亡情况,免疫组织化学法检测肿瘤组织中微血管密度,检测EGFR/PI3K/Akt及HIF-1α/VEGF信号通路信使核糖核酸(mRNA)和蛋白的表达。两组间比较采用独立样本t检验。结果:放疗的抑瘤率为43.44%,实验组移植瘤体积和重量低于对照组(0.669±0.042比0.273±0.076,t=15.798,P<0.05;22.24±1.37比16.83±2.06,t=13.375,P<0.05),实验组细胞凋亡率高于对照组(5.22±0.64比38.76±5.19,t=22.218,P<0.05),实验组的组织微血管密度低于对照组(21.56±2.48比12.25±3.04,t=8.220,P<0.05),实验组的瘤组织中EGFR/PI3K/Akt及HIF-1α/VEGF mRNA与蛋白表达水平低于对照组。结论:放疗可以显著抑制Lewis肺癌移植瘤增殖,促进其凋亡,并下调EGFR/PI3K/Akt及HIF-1α/VEGF信号通路的表达。Objective:To establish a Lewis lung cancer mouse model and investigate the inhibitory effect of radiotherapy on tumors,as well as its effects on Epidermal growth factor receptor/phosphatidylinositol 3-kinase/serine-threonine kinase(EGFR/PI3K/Akt)and hypoxiainducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)signaling pathway expression.Methods:A total of 24 specific pathogen-free C57BL/6 mice were inoculated with Lewis lung cancer cells to establish Lewis lung cancer mouse models.The mice were randomly divided into control group and experimental group,with 12 mice in each group.The control group did not receive radiotherapy,while the experimental group began receiving 6MV X-ray radiotherapy on the 14th day after inoculation.After radiotherapy,the mice were euthanized and dissected,tumor suppression rate was calculated,tissue pathology with hematoxylin-eosin staining(HE)staining and cell apoptosis with TdT-mediated dUTP nick end labeling(TUNEL)staining were observed,microvascular density in tumor tissue was detected by immunohistochemistry,and the expression of messenger ribo nucleic acid(mRNA)and proteins of EGFR/PI3K/Akt and HIF-1α/VEGF signaling pathway was detected.Independent sample t test was used for comparison between the two groups.Results:The tumor inhibition rate of radiotherapy was 43.44%.The volume and weight of transplanted tumors in the experimental group were lower than those in the control group(0.669±0.042 vs.0.273±0.076,t=15.798,P<0.05;22.24±1.37 vs.16.83±2.06,t=13.375,P<0.05).The apoptosis rate of the experimental group was higher than that of the control group(5.22±0.64 vs.38.76±5.19,t=22.218,P<0.05).The microvessel density of the experimental group was lower than that of the control group(21.56±2.48 vs.12.25±3.04,t=8.220,P<0.05).The mRNA and protein expression levels of EGFR/PI3K/Akt and HIF-1α/VEGF in the tumor tissues of the experimental group were lower than those of the control group.Conclusion:Radiation therapy can significantly inhibit the proliferation of Lew

关 键 词：肺癌 增殖 血管内皮生长因子 血管增生 放疗 

分 类 号：R734.2[医药卫生—肿瘤]