DLK1调控ERK1/2信号通路介导宫颈癌放疗抵抗作用机制  

Mechanism of mediates cervical cancer radiotherapy resistance by DLK1 regulates ERK1/2 signal pathway

作　　者：袁丽 鲁选文[2] 陈宇[3] YUAN Li;LU Xuan-wen;CHEN Yu(The First Clinical College,Hubei Medical College,Shiyan 442000;Department of Obstetrics and Gynecology,Taihe Hospital,Shiyan 442000;Department of Oncology,Taihe Hospital,Shiyan 442000,China)

机构地区：[1]湖北医药学院第一临床学院,湖北十堰442000 [2]太和医院妇产科,湖北十堰442000 [3]太和医院肿瘤科,湖北十堰442000

出　　处：《生物技术》2022年第4期471-475,共5页Biotechnology

摘　　要：[目的]分析DLK1及其调控的下游ERK1/2信号转导通路在宫颈癌放疗抵抗中所起到的作用及机制。[方法]取Hela细胞、放射抗拒的Hela细胞、Siha细胞和放射抗拒的Siha细胞分别记为Hela组、Hela-R组、Siha组和Siha-R组;各组细胞开始接受Varian Unique设备的2Gy的X线照射,剂量率2 Gy/min,累计照射6次;放疗前后显微镜下观察Hela、Hela-R、Siha和Siha-R的细胞形态,在放射照射前、照射2次和照射4次时,计算细胞存活分数;照射3次和照射6次后采用流式细胞术检测细胞凋亡率;照射6次后检测细胞中DLK1、ERK1/2、MEK1/2、Raf、GAPDH蛋白和mRNA表达水平。[结果]亲本细胞细胞连接紧密,呈卵圆形铺路石样,符合上皮表型,放疗抵抗细胞株呈梭形或长条形,细胞株细胞间距加大,纤维细胞表型;不同照射剂量时Hela-R组、Siha-R组细胞存活分数均明显高于Hela组和Siha组(P<0.05);不同照射剂量时Hela-R组、Siha-R组细胞凋亡率均明显低于Hela组和Siha组(P<0.05);Hela-R组、Siha-R组细胞DLK1、ERK1/2、MEK1/2、Raf蛋白及mRNA表达水平均明显高于Hela组和Siha组(P<0.05)。[结论]DLK1可激活ERK1/2信号通路并介导宫颈癌放疗抵抗的发生。[Objective]To analyze the role of DLK1 and its downstream ERK1/2 signal transduction pathway in cervical cancer radiotherapy resistance and its mechanism.[Method]Hela cells,radioresistant Hela cells,Siha cells,and radioresistant Siha cells were denoted as Hela group,Hela-R group,Siha group and Siha-R group,respectively;each group of cells began to receive 2Gy X from the Varian Unique device radiation irradiation,dose rate 2 Gy/min,cumulative irradiation 6 times;before and after radiotherapy,observe the cell morphology of Hela,Hela-R,Siha and Siha-R under a microscope.Before radiation irradiation,when irradiating 2 times and irradiating 4 times,calculate the cell survival score;after 3 irradiations and 6 irradiations,the apoptosis rate was detected by flow cytometry;after 6 irradiations,the protein and mRNA expression levels of DLK1,ERK1/2,MEK1/2,Raf,GAPDH in the cells were detected.[Result]The parental cells were tightly connected,showing oval paving stones,conforming to the epithelial phenotype,the radiotherapy-resistant cell lines were fusiform or elongated,the cell line spacing increased,and the fibrocyte phenotype;Hela-The cell survival scores of R group and Siha-R group were significantly higher than that of Hela group and Siha group(P<0.05);the apoptosis rate of Hela-R group and Siha-R group were both significantly lower than Hela group and Siha group(P<0.05);Hela-R group,Siha-R group cells protein and mRNA levels of DLK1,ERK1/2,MEK1/2,Raf were significantly higher than Hela group and Siha group(P<0.05).[Conclusion]DLK1 can activate the ERK1/2 signaling pathway and mediate the occurrence of cervical cancer radiotherapy resistance.

关 键 词：DLK1 ERK1/2信号通路 宫颈癌 放疗抵抗 

分 类 号：R737.33[医药卫生—肿瘤]