Xie Kejie, Ni Xiaoyan, Lv Shanmei, Zhou Guozhong, He Honger
Department of Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China.
Department of Radiotherapy, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China.
Oncol Lett. 2021 May;21(5):365. doi: 10.3892/ol.2021.12626. Epub 2021 Mar 10.
Non-small cell lung cancer (NSCLC) is a common malignant tumor. ERCC excision repair 1 endonuclease non-catalytic subunit (ERCC1) is a key mediator of nucleotide excision repair. The present study aimed to explore the synergistic effects of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib combined with on the sensitivity of NSCLC cells to cisplatin. Preliminary experiments were performed to identify the optimal concentrations of cisplatin and olaparib for cellular treatment and subsequently NCI-H1299 and SK-MES-1 cells were treated with 20 µg/ml cisplatin combined with 50 µg/ml olaparib and 50 µg/ml cisplatin combined with 70 µg/ml olaparib, respectively. Subsequently, transfections were carried out to overexpress or knockdown the expression of in NSCLC cell lines, including NCI-H1299 and SK-MES-1. The transfection efficiency was evaluated using reverse transcription-quantitative PCR and western blotting. The results demonstrated that cells with overexpression and knockdown were successfully constructed. Finally, the cell viability and apoptosis were determined using the Cell Counting Kit-8 and Annexin V-FITC cell apoptosis assays, respectively. In NCI-H1299 or SK-MES-1 cells treated with cisplatin combined with olaparib for 24 h, the cell viability significantly increased following overexpression compared with the GV230 group (P<0.05), but significantly inhibited following knockdown compared with the siRNA-NC group (P<0.05). However, ERCC1 overexpression or knockdown had the opposite effect on apoptosis. In conclusion, olaparib combined with expression may enhance the sensitivity of cisplatin in NSCLC. These findings may provide novel insight for the improvement of platinum drug sensitivity and treatment of NSCLC.
非小细胞肺癌（NSCLC）是一种常见的恶性肿瘤。ERCC切除修复1核酸内切酶非催化亚基（ERCC1）是核苷酸切除修复的关键介质。本研究旨在探讨聚（ADP-核糖）聚合酶（PARP）抑制剂奥拉帕利联合[此处原文缺失相关内容]对NSCLC细胞对顺铂敏感性的协同作用。进行初步实验以确定用于细胞处理的顺铂和奥拉帕利的最佳浓度，随后分别用20μg/ml顺铂联合50μg/ml奥拉帕利和50μg/ml顺铂联合70μg/ml奥拉帕利处理NCI-H1299和SK-MES-1细胞。随后，进行转染以在NSCLC细胞系（包括NCI-H1299和SK-MES-1）中过表达或敲低[此处原文缺失相关内容]的表达。使用逆转录定量PCR和蛋白质印迹法评估转染效率。结果表明成功构建了[此处原文缺失相关内容]过表达和敲低的细胞。最后，分别使用细胞计数试剂盒-8和膜联蛋白V-FITC细胞凋亡检测法测定细胞活力和凋亡情况。在用顺铂联合奥拉帕利处理24小时的NCI-H1299或SK-MES-1细胞中，与GV230组相比，[此处原文缺失相关内容]过表达后细胞活力显著增加（P<0.05），但与siRNA-NC组相比，[此处原文缺失相关内容]敲低后细胞活力显著受到抑制（P<0.05）。然而，ERCC1过表达或敲低对凋亡有相反的影响。总之，奥拉帕利联合[此处原文缺失相关内容]表达可能增强NSCLC对顺铂的敏感性。这些发现可能为提高铂类药物敏感性和治疗NSCLC提供新的见解。
