Bi Yawei, Cao Kun, Wang Yuan, Yang Wei, Ma Na, Lei Xiao, Chen Yuanyuan
Department of Gastroenterology and Hepatology, The First Medical Center of PLA General Hospital, Beijing 100859, China.
Department of Radiation Medicine, Faculty of Naval Medicine, Naval Military Medical University, Shanghai 200433, China.
J Oncol. 2023 Mar 3;2023:5636852. doi: 10.1155/2023/5636852. eCollection 2023.
NSCLC (non-small-cell lung cancer) is an aggressive form of lung cancer and accompanies high morbidity and mortality. This study investigated the function and associated mechanism of MMP10 during radiotherapy of NSCLC. MMP10 expression in patients and their overall survival rate were assessed through GEPIA. Protein expression was tested by western blotting. Radioresistance was detected by apoptosis and clonogenic assay. The extent of DNA damage and repair was revealed by the comet test and H2AX foci test. High MMP10 levels in specimens of lung adenocarcinoma were related to poor patient outcomes. Clonogenic and apoptosis assays revealed that MMP10 knockdown in A549 cells initiated radiosensitization. Furthermore, MMP10 siRNA increased damage to the DNA in NSCLC cells, while MMP10 was observed to participate in DNA damage repair post-ionizing radiation. Thus, after irradiation, MMP10 plays an essential role in NSCLC through the repair pathway of DNA damage; regulating MMP10 for NSCLC radiosensitivity might have potential treatment implications in radiotherapy of NSCLC.
非小细胞肺癌（NSCLC）是一种侵袭性肺癌，发病率和死亡率都很高。本研究调查了基质金属蛋白酶10（MMP10）在NSCLC放疗过程中的作用及相关机制。通过GEPIA评估患者体内MMP10的表达及其总生存率。采用蛋白质免疫印迹法检测蛋白质表达。通过细胞凋亡和克隆形成试验检测放射抗性。通过彗星试验和H2AX焦点试验揭示DNA损伤和修复的程度。肺腺癌标本中高MMP10水平与患者预后不良有关。克隆形成试验和细胞凋亡试验表明，A549细胞中MMP10基因敲低可引发放射增敏作用。此外，MMP10小干扰RNA（siRNA）增加了NSCLC细胞中的DNA损伤，而MMP10被观察到参与电离辐射后DNA损伤的修复。因此，照射后，MMP10通过DNA损伤修复途径在NSCLC中发挥重要作用；调节MMP10以提高NSCLC放射敏感性可能对NSCLC放疗具有潜在的治疗意义。
