Tang Jianming, Cao Yu, Zhang Hong, Wang Rui
The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Arch Med Sci. 2023 Jan 5;20(5):1631-1654. doi: 10.5114/aoms/158533. eCollection 2024.
Lung cancer is the leading cause of cancer-associated mortality globally. In particular, non-small cell lung cancer (NSCLC) constitutes the largest percentage of all cases of lung cancer. In clinical practice, radioresistance contributes to poor responses to radiotherapy. Therefore, the demand remains to explore potential novel and effective mechanism underlying radioresistance to improve the efficacy of radiotherapy for NSCLC.
Western blotting was conducted to quantify the protein expression of epithelial-mesenchymal transition markers E-cadherin and vimentin in the A549 cell line. The proliferation of A549 cells was measured using the Cell Counting Kit-8 and colony forming assays. In addition, the apoptosis of A549 cells was analyzed by flow cytometry. Invasion and migration by NSCLC cells were quantified using Transwell and wound healing assays. Plasmids were used to overexpress decoy receptor 3 (DcR3) in A549 cells. Xenograft models were established to measure the extent of NSCLC tumor growth .
Our study clarified the activation of the DcR3/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK-3β) pathway in radioresistant NSCLC cells. Oxymatrine (OMT) treatment restored radiosensitivity and inhibited irradiation-induced epithelial-mesenchymal transition (EMT), invasion and migration in NSCLC cells through the DcR3/AKT/GSK-3β pathway . By contrast, OMT treatment promoted the suppressive effects of radiation on the weight and volume of the xenograft tumors in animal models.
OMT suppressed the development of radioresistance in NSCLC cells by promoting radiosensitivity, through the reversal of EMT process by inhibiting the DcR3/AKT/GSK-3β pathway.
肺癌是全球癌症相关死亡的主要原因。特别是，非小细胞肺癌（NSCLC）在所有肺癌病例中占比最大。在临床实践中，放射抗性导致放疗反应不佳。因此，仍需要探索潜在的新型有效机制来改善NSCLC放疗疗效。
采用蛋白质免疫印迹法对A549细胞系中上皮-间质转化标志物E-钙黏蛋白和波形蛋白的蛋白表达进行定量。使用细胞计数试剂盒-8和集落形成试验检测A549细胞的增殖。此外，通过流式细胞术分析A549细胞的凋亡情况。使用Transwell和伤口愈合试验对NSCLC细胞的侵袭和迁移进行定量。利用质粒在A549细胞中过表达诱饵受体3（DcR3）。建立异种移植模型以测量NSCLC肿瘤生长程度。
我们的研究阐明了放射抗性NSCLC细胞中DcR3/蛋白激酶B（AKT）/糖原合酶激酶3β（GSK-3β）通路的激活。氧化苦参碱（OMT）处理通过DcR3/AKT/GSK-3β通路恢复了放射敏感性，并抑制了NSCLC细胞中辐射诱导的上皮-间质转化（EMT）、侵袭和迁移。相比之下，OMT处理增强了辐射对动物模型中异种移植肿瘤重量和体积的抑制作用。
OMT通过抑制DcR3/AKT/GSK-3β通路逆转EMT过程，促进放射敏感性，从而抑制NSCLC细胞中放射抗性的发展。
