Yao Yuanhu, Qiu Xiangnan, Chen Meng, Qin Zhaohui, Zhang Xinjun, Zhang Wei
Department of Radiation Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
Department of Radiation Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Curr Mol Med. 2025;25(3):353-360. doi: 10.2174/0115665240280822231221060656.
Radiosensitivity remains an important factor affecting the clinical outcome of radiotherapy for non-small cell lung cancer (NSCLC). Liver kinase B1 (LKB1) as a tumor suppressor, is one of the most commonly mutated genes in NSCLC. However, the role of LKB1 on radiosensitivity and the possible mechanism have not been elucidated in the NSCLC. In this study, we investigated the regulatory function of LKB1 in the radiosensitivity of NSCLC cells and its possible signaling pathways.
After regulating the expression of LKB1, cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assay. The flow cytometry assay was used to analyse cell cycle distribution. Survival fraction and sensitization enhancement ratio (SER) were generated by clonogenic survival assay. Western blot analysis was used to assess expression levels of LKB1, p53, p21, γ-H2AX and p-Chk2.
Our study found that when the NSCLC cells were exposed to ionizing radiation, LKB1 could inhibit NSCLC cell proliferation by promoting DNA double strand break and inducing DNA repair. In addition, LKB1 could induce NSCLC cells G1 and G2/M phase arrest through up-regulating expression of p53 and p21 proteins.
This current study demonstrates that LKB1 enhances the radiosensitivity of NSCLC cells via inhibiting NSCLC cell proliferation and inducing G2/M phase arrest, and the mechanism of cell cycle arrest associated with signaling pathways of p53 and p21 probably.
放射敏感性仍然是影响非小细胞肺癌（NSCLC）放射治疗临床结果的重要因素。肝激酶B1（LKB1）作为一种肿瘤抑制因子，是NSCLC中最常发生突变的基因之一。然而，LKB1在NSCLC放射敏感性中的作用及可能机制尚未阐明。在本研究中，我们探讨了LKB1在NSCLC细胞放射敏感性中的调控作用及其可能的信号通路。
调节LKB1表达后，采用细胞计数试剂盒-8（CCK-8）法检测细胞增殖。采用流式细胞术分析细胞周期分布。通过克隆形成存活试验得出存活分数和增敏增强率（SER）。采用蛋白质免疫印迹分析评估LKB1、p53、p21、γ-H2AX和p-Chk2的表达水平。
我们的研究发现，当NSCLC细胞暴露于电离辐射时，LKB1可通过促进DNA双链断裂和诱导DNA修复来抑制NSCLC细胞增殖。此外，LKB1可通过上调p53和p21蛋白的表达诱导NSCLC细胞G1期和G2/M期阻滞。
本研究表明，LKB1通过抑制NSCLC细胞增殖和诱导G2/M期阻滞来增强NSCLC细胞的放射敏感性，细胞周期阻滞机制可能与p53和p21信号通路有关。
