Shan Jiaojiao, Wang Xinfeng, Zhao Jie
Department of Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine Ji'nan 250014, Shandong, China.
Department of Pharmacy, The Third Affiliated Hospital of Shandong First Medical University Ji'nan 250031, Shandong, China.
Am J Transl Res. 2022 Jun 15;14(6):3783-3795. eCollection 2022.
This study aimed to reveal the role and mechanism of X-ray repair cross complementing 2 (XRCC2) and bevacizumab combined with radiotherapy in the treatment of non-small cell lung cancer (NSCLC).
Gene Expression Profiling Interactive Analysis (GEPIA) database and Starbase database were used to predict the expression level of XRCC2 in NSCLC tissues and the survival time of patients diagnosed with NSCLC, respectively. Besides, qRT-PCR (quantitative real time polymerase chain reaction) and immunoblotting were conducted to confirm the expression of XRCC2 NSCLC tissues and cells. Moreover, cell viability and colony formation were measured by CCK-8 (cell counting kit-8) assay. Cell migration and invasion capabilities were determined by transwell assay. Flow cytometry analysis was employed to detect cell cycle.
XRCC2 was highly expressed in NSCLC tissues and cells. Additionally, bevacizumab combined with radiotherapy significantly inhibited NSCLC cell proliferation, migration and invasion. Knockdown of XRCC2 further aggravated the role of bevacizumab and radiotherapy in NSCLC, while XRCC2 overexpression reversed these effects efficiently. Furthermore, XRCC2 silence exacerbated the arrest of cell cycle induced by bevacizumab combined with radiotherapy in NSCLC cells, whereas overexpression of XRCC2 alleviated the arrest remarkably.
Collectively, our research revealed that XRCC2 inhibited the sensitivity of NSCLC to bevacizumab combined with radiotherapy by decreasing cell cycle arrest.
本研究旨在揭示X射线修复交叉互补蛋白2（XRCC2）及贝伐单抗联合放疗在非小细胞肺癌（NSCLC）治疗中的作用及机制。
分别利用基因表达谱交互分析（GEPIA）数据库和Starbase数据库预测NSCLC组织中XRCC2的表达水平及NSCLC确诊患者的生存时间。此外，进行qRT-PCR（定量实时聚合酶链反应）和免疫印迹以确认XRCC2在NSCLC组织和细胞中的表达。而且，通过CCK-8（细胞计数试剂盒-8）检测法测定细胞活力和集落形成。采用Transwell检测法确定细胞迁移和侵袭能力。运用流式细胞术分析检测细胞周期。
XRCC2在NSCLC组织和细胞中高表达。此外，贝伐单抗联合放疗显著抑制NSCLC细胞增殖、迁移和侵袭。敲低XRCC2进一步加重了贝伐单抗和放疗在NSCLC中的作用，而XRCC2过表达有效逆转了这些作用。此外，XRCC2沉默加剧了贝伐单抗联合放疗诱导的NSCLC细胞周期阻滞，而XRCC2过表达显著减轻了这种阻滞。
总体而言，我们的研究表明XRCC2通过减少细胞周期阻滞抑制NSCLC对贝伐单抗联合放疗的敏感性。
