摘要
目的:分析不同强度有氧运动对肺腺癌吉非替尼获得性耐药的影响,并探讨其潜在机制及临床意义.方法:建立由吉非替尼诱导的肺腺癌耐药细胞系PC-9-GR.通过ROS相关指标试剂盒、Western blot及流式细胞术检测亲本细胞系PC-9与耐药细胞系PC-9-GR中ROS相关指标、缺氧诱导因子1(HIF-1)与乙醛脱氢酶1(ALDH1)蛋白及肿瘤干细胞(CSCs)百分比.将裸鼠分为8组,皮下种植耐药细胞系PC-9-GR,成瘤后分别进行不同强度有氧运动,或不同强度有氧运动联合吉非替尼药物治疗,对比各组细胞皮下成瘤能力及对吉非替尼的应答效力;并检测各组裸鼠血清或瘤体内ROS相关指标、HIF-1与ALDH1蛋白及CSCs百分比.结果:成功建立肺腺癌耐药细胞系PC-9-GR.与PC-9相比,PC-9-GR中ROS与MDA含量增加,而SOD活性降低,且HIF-1与ALDH1蛋白及CSCs百分比均增高(P<0.05).裸鼠皮下荷瘤实验中,与对照组相比,吉非替尼单药组成瘤能力无明显差异,而低、中及高强度有氧运动组则逐渐降低(P<0.05);与吉非替尼单药组相比,低、中及高强度有氧运动联合吉非替尼组成瘤能力逐渐降低(P<0.05);与不同强度有氧运动组相比,不同强度有氧运动联合吉非替尼组成瘤能力显著降低(P<0.05).结论:有氧运动可增强耐药细胞对吉非替尼的应答效力,可作为肺腺癌治疗中的有效辅助措施,为肺腺癌的临床治疗提供新思路和有效治疗手段.
Objective:To analyze the effect of aerobic exercise of different intensity on acquired resistance of gefitinib in lung adenocarcinoma,and to explore its potential mechanism and clinical significance.Methods:Lung adenocarcinoma PC-9-GR cell line induced by gefitinib was established.ROS related indicators in PC-9 and PC-9-GR were detected by ROS-related index kit.The level of HIF-1 and ALDH1 protein and the percentage of cancer stem cells(CSCs)in PC-9 cells and PC-9-GR cells were determined by Western blot and flow cytometry,respectively.The nude mice were divided into 8 groups and subcutaneously implanted with drug-resistant cell line PC-9-GR.After tumor formation,aerobic exercise of different intensity was performed,or aerobic exercise of different intensity combined with gefitinib therapy was performed.The subcutaneous tumorigenesis ability and response to gefitinib of mice in each group were compared.The contents of ROS related indicators,the level of HIF-1 and ALDH1 protein,and the percentage of CSCs in serum or tumor body of nude mice were detected.Results:Drug-resistant lung adenocarcinoma cell line PC-9-GR was established successfully.Compared with the parent cell line,the contents of ROS and MDA in PC-9-GR cells were significantly increased,while the activity of SOD was significantly decreased,the level of HIF-1 and ALDH1 protein and the percentage of CSCs were significantly increased(P<0.05).In the subcutaneous tumor bearing experiment of nude mice,compared with the control group,there was no significant difference in tumor formation ability of the gefitinib monotherapy group,but it was gradually decreased in aerobic exercise of low,medium and high intensity groups(P<0.05).Compared with the gefitinib monotherapy group,the tumor formation ability of aerobic exercise of low,medium and high intensity combined with gefitinib therapy groups were gradually decreased(P<0.05).Compared with aerobic exercise of different intensity groups,the tumor formation ability of aerobic exercise of different intensity combined with gefitinib therapy groups were significantly decreased(P<0.05).Conclusion:Aerobic exercise enhanced the response of drug-resistant cells to gefitinib,and could be used as an effective adjuvant measure in the treatment of lung adenocarcinoma,providing a new idea and effective manner for the clinical treatment of lung adenocarcinoma.
作者
杨洪
刘怡文
孔金玉
YANG Hong;LIU Yiwen;KONG Jinyu(School of Physical Education.Henan University of Science and Technology,Luoyang 471000,China;Cancer Hospital,the First Affiliated Hospital(College of Clinical Medicine)of Henan University of Science and Technology,Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment,Henan Key Laboratory of Cancer Epigenetics,Luoyang 471003,China)
出处
《暨南大学学报（自然科学与医学版）》
CAS
CSCD
北大核心
2021年第6期589-599,共11页
Journal of Jinan University(Natural Science & Medicine Edition)
基金
河南省科技攻关项目(202102310321,202102310129,212102310670)。
关键词
有氧运动
肺腺癌
吉非替尼
获得性耐药
肿瘤干细胞
aerobic exercises
lung adenocarcinoma
gefitinib
acquired drug resistance
cancer stem cells(CSCs)
