An Suhong, Xu Xiaoping, Bao Yanhong, Su Fang, Jiang Yiqian
Department of Radiotherapy, Xiaoshan Hospital Affiliated to Wenzhou Medical University, China.
Department of Radiotherapy, Xiaoshan Hospital Affiliated to Wenzhou Medical University, China.
Tissue Cell. 2024 Dec;91:102577. doi: 10.1016/j.tice.2024.102577. Epub 2024 Sep 30.
The management of non-small cell lung cancer (NSCLC) often includes the use of radiotherapy, with individual outcomes being impacted by the tumor's response to this treatment modality. Cephalomannine (CPM), a taxane diterpenoid found in Taxus spp, has been found to have anti-tumor activity. This study was aim to the explore the role and mechanism by which CPM affects radiotherapy resistance in NSCLC.
H460 cells were pretreated with different doses of CPM. H460 cells were transfected with β-catenin overexpression plasmids. The cell viability, colony-forming ability, migration ability, and sphere-forming ability and apoptosis of the cells were measured by using CCK-8, colony-forming, transwell, and sphere-forming assay and flow cytometry. Western blot assay was employed to detect the expression of β-catenin and BMP2.
The cell viability, proliferation, migration and sphere-forming ability of cells in the radiotherapy-resistant (RR) group were significantly higher than those in the radiotherapy-sensitivity (RS) group. Conversely, the apoptosis rate of cells in the RR group was lower than that in the RS group. However, after CPM pretreatment of RR group cells, the above phenomena were reversed in a CPM dose-dependent manner. Subsequently, pretreatment with CPM resulted in a decrease in the expression levels of β-catenin and BMP2 in the RR group. In addition, overexpression of β-catenin mitigated the inhibitory effects of CPM on radiotherapy-resistant NSCLC cells.
CPM has the potential to decrease radiotherapy resistance in NSCLC cells by inhibiting the β-catenin-BMP2 signaling pathway, promoting apoptosis, and ultimately impeding cell growth.
非小细胞肺癌（NSCLC）的治疗通常包括放射治疗，肿瘤对这种治疗方式的反应会影响个体治疗结果。头状紫杉碱（CPM）是从红豆杉属植物中发现的一种紫杉烷二萜，已被发现具有抗肿瘤活性。本研究旨在探讨CPM影响NSCLC放疗抵抗的作用及机制。
用不同剂量的CPM预处理H460细胞。用β-连环蛋白过表达质粒转染H460细胞。采用CCK-8法、集落形成法、Transwell法、成球实验和流式细胞术检测细胞活力、集落形成能力、迁移能力、成球能力及细胞凋亡情况。采用蛋白质免疫印迹法检测β-连环蛋白和骨形态发生蛋白2（BMP2）的表达。
放疗抵抗（RR）组细胞的活力、增殖、迁移及成球能力显著高于放疗敏感（RS）组。相反，RR组细胞的凋亡率低于RS组。然而，用CPM预处理RR组细胞后，上述现象呈CPM剂量依赖性逆转。随后，CPM预处理导致RR组中β-连环蛋白和BMP2的表达水平降低。此外，β-连环蛋白的过表达减轻了CPM对放疗抵抗的NSCLC细胞的抑制作用。
CPM有可能通过抑制β-连环蛋白-BMP2信号通路、促进细胞凋亡并最终阻碍细胞生长来降低NSCLC细胞的放疗抵抗。
