Department of Oncology, The First People's Hospital of Qujing, The Qujing Affiliated Hospital of Kunming Medical University, Qujing, Yunnan, 655000, China.
Department of Thoracic Surgery, The First People's Hospital of Qujing, The Qujing Affiliated Hospital of Kunming Medical University, Qujing, Yunnan, 655000, China.
Am J Med Sci. 2024 Nov;368(5):503-517. doi: 10.1016/j.amjms.2024.06.027. Epub 2024 Jun 27.
Non-small cell lung cancer (NSCLC) is a pernicious tumor with high incidence and mortality rates. The incidence rate of NSCLC increases with age and poses a serious danger to human health. The aim of this study was to determine the mechanism by which (-)-epicatechin (EC) alleviates NSCLC.
Twenty-four pairs of NSCLC tissues and cancer-adjacent tissues were collected, and A549 and H460 radiotherapy-resistant strains were generated by repeatedly irradiating A549 and H460 cells with dose-gradient X-rays. Radiotherapy-resistant H460 cells were successfully injected subcutaneously into the left dorsal side of nude mice at a dose of 1 × 10 to establish an NSCLC animal model. The levels of interrelated genes and proteins were detected by RT‒qPCR and Western blotting, and cell proliferation and apoptosis were evaluated by CCK‒8 assay, Transwell assay, flow cytometry, and TUNEL staining.
LOC107986454 was highly expressed in NSCLC patients, while miR-143-3p was expressed at low levels and was negatively correlated with LOC107986454. Functionally, EC promoted autophagy and apoptosis induced by radiotherapy, restrained cell proliferation and migration, and ultimately enhanced the radiosensitivity of NSCLC cells. A downstream mechanistic study showed that EC facilitated miR-143-3p expression by inhibiting LOC107986454 and then restraining the expression of EZH2, which ultimately facilitated autophagy and apoptosis in cancer cells, inhibited proliferation and migration, and enhanced the radiosensitivity of NSCLC cells.
EC can enhance the radiosensitivity of NSCLC cells by regulating the LOC107986454/miR-143-3p/EZH2 axis.
非小细胞肺癌（NSCLC）是一种恶性肿瘤，具有较高的发病率和死亡率。NSCLC 的发病率随年龄增长而增加，严重威胁人类健康。本研究旨在探讨（-）-表儿茶素（EC）缓解 NSCLC 的作用机制。
收集 24 对 NSCLC 组织及其癌旁组织，采用剂量梯度 X 射线反复照射 A549 和 H460 细胞，构建 A549 和 H460 放疗耐药株。将 1×10 剂量的 H460 放疗耐药细胞成功注射到裸鼠左侧背部皮下，建立 NSCLC 动物模型。采用 RT‒qPCR 和 Western blot 检测相关基因和蛋白水平，CCK‒8 检测细胞增殖，Transwell 检测细胞迁移，流式细胞术和 TUNEL 染色检测细胞凋亡。
LOC107986454 在 NSCLC 患者中高表达，miR-143-3p 表达水平较低，与 LOC107986454 呈负相关。功能研究表明，EC 通过促进放疗诱导的自噬和细胞凋亡，抑制细胞增殖和迁移，增强 NSCLC 细胞的放射敏感性。进一步的机制研究表明，EC 通过抑制 LOC107986454 促进 miR-143-3p 的表达，进而抑制 EZH2 的表达，促进癌细胞自噬和凋亡，抑制增殖和迁移，增强 NSCLC 细胞的放射敏感性。
EC 可通过调节 LOC107986454/miR-143-3p/EZH2 轴增强 NSCLC 细胞的放射敏感性。
