摘要
目的探究微小RNA(miR)-1246对肺癌细胞放疗敏感性的调控及对放疗所致肺损伤的影响。方法收集肺癌患者肺癌及癌旁组织,通过逆转录PCR(RT-qPCR)检测miR-1246水平。将肺癌细胞A549分为阴性对照(NC)组和抑制剂组,分别转染miR-1246NC和抑制剂质粒,40只小鼠分为NC组、放疗组、抑制剂组和抑制剂+放疗组,并通过尾静脉注射miR-1246抑制剂(4×10^(7) TU,300μL)持续抑制miR-1246表达。在建模第14天于肿瘤部位行局部放疗,每天1次,连续2周。分析肿瘤生长情况,并检测肿瘤组织的增殖、凋亡情况及β-catenin蛋白表达水平。通过苏木素-伊红(HE)染色分析肺损伤情况,检测各组小鼠肺组织丙二醛(MDA)、超氧化物歧化酶(SOD)、炎性指标和miR-1246表达水平。结果肺癌组织miR-1246相对表达水平高于癌旁组织[(3.47±0.64)vs.(1.42±0.31)],差异有统计学意义(P<0.05)。放疗组和抑制剂组第28天肿瘤组织体积及质量、肿瘤组织miR-1246相对表达水平、CyclinD1、Ki-67、Bcl-2和β-catenin蛋白水平低于NC组,高于抑制剂+放疗组,而Bax蛋白水平高于NC组,低于抑制剂+放疗组(P<0.05)。放疗组肺组织损伤程度、MDA、炎性指标和肺组织miR-1246相对表达水平高于NC组和抑制剂组,而抑制剂+放疗组上述指标均低于放疗组(P<0.05)。结论miR-1246可能通过抑制β-catenin表达来提高肺癌对放疗的敏感性,降低miR-1246水平可缓解由放射线诱导的正常肺组织损伤。
Objective To explore the regulation of microRNA(miR)-1246 on the sensitivity of lung cancer cells to radiotherapy and its influence on lung injury caused by radiotherapy.Methods Collected lung cancer and adjacent tissues,and detected the level of miR-1246 by reverse transcription PCR(RT-qPCR).The lung cancer cells A549 were divided into the negative control(NC)group and the inhibitor group,and were transfected with miR-1246NC and inhibitor plasmid,respectively.A total of 40 mice were divided into the NC group,the radiotherapy group,the inhibitor group and the inhibitor+radiotherapy group,miR-1246 inhibitor(4×10^(7) TU,300μL)was injected through the tail vein to continuously inhibit the expression of miR-1246.Local radiotherapy was performed at the tumor site on the 14th day of modeling,once a day for 2 consecutive weeks.Analyzed tumor growth,and detected tumor tissue proliferation,apoptosis andβ-catenin protein expression level.The lung injury was analyzed by hematoxylin-eosin(HE)staining,and the expression levels of malondialdehyde(MDA),superoxide dismutase(SOD),inflammatory indicators and miR-1246 in the lung tissues of each group of mice were detected.Results The level of miR-1246 in lung cancer tissue was higher than that in adjacent tissues[(3.47±0.64)vs.(1.42±0.31)],the difference was statistically significant(P<0.05).Tumor volume and mass at 28th day,the expression level of miR-1246,CyclinD1,Ki-67,Bcl-2 andβ-catenin protein levels of the tumor tissues in the radiotherapy group and the inhibitor group were lower than those in the NC group,but higher than those in the inhibitor+radiotherapy group,while the Bax protein was higher than that in the NC group,but lower than that in the inhibitor+radiotherapy group(P<0.05).The lung tissue damage degree,MDA,inflammatory index and miR-1246 expression level of the lung tissue in the radiotherapy group were higher than those in the NC group and the inhibitor group,while the above indicators in the inhibitor+radiotherapy group were lower than those in the radiotherapy group(P<0.05).Conclusion miR-1246 may increase the sensitivity of lung cancer to radiotherapy by inhibiting the expression ofβ-catenin,reducing miR-1246 level can alleviate radiation-induced normal lung tissue damage.
作者
楚丽
要雪品
梁艳
段颖欣
姜溪
王力军
CHU Li;YAO Xuepin;LIANG Yan;DUAN Yingxin;JIANG Xi;WANG Lijun(Department of Radiotherapy and Chemotherapy,the Second Affiliated Hospital of Xingtai Medical College,Xingtai,Hebei 054000,China)
出处
《重庆医学》
CAS
2021年第17期2900-2905,2911,共7页
Chongqing medicine
基金
河北省邢台市科技计划项目(2019ZC234)。
作者简介
楚丽(1982-),主治医师,硕士,主要从事肿瘤放疗研究。
