Department of Emergency, Fujian Provincial Hospital, 134 East Street, Fuzhou, 350001, Fujian, People's Republic of China.
Shengli Clinical Medical College of Fujian Medical University, 134 East Street, Fuzhou, 350001, Fujian, People's Republic of China.
Sci Rep. 2022 Jul 6;12(1):11462. doi: 10.1038/s41598-022-15643-3.
Lung cancer is the most malignant form of cancer and has the highest morbidity and mortality worldwide. Due to drug resistance, the current chemotherapy for lung cancer is not effective and has poor therapeutic effects. Tripchlorolide (T4), a natural extract from the plant Tripterygium wilfordii, has powerful immunosuppressive and antitumour effects and may become a potential therapeutic agent for lung cancer. Therefore, this study aimed to investigate the effect of T4 on reducing chemoresistance in lung cancer cells and to explore the mechanism. 1. A549 and A549/DDP cells were separately transfected with AEG-1 overexpression and AEG-1 knockdown plasmids. A549/DDP cells were divided into the A549/DDP empty group, T4 group, and T4 + AEG-1 overexpression group. A CCK-8 assay was used to evaluate the proliferation of cells in each group. RT-qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1. Expression of AEG-1 in A549 and A549/DDP cells was positively correlated with cisplatin resistance. When the AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P < 0.05). After the AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied. The lethal effect was significantly increased compared to that in the corresponding control cells (all P < 0.05). AEG-1 protein expression gradually decreased with increasing T4 concentration in A549 and A549/DDP cells. Resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P < 0.05), and this effect was enhanced after transfection with the AEG-1 knockdown plasmid. T4 plays an important role in increasing the sensitivity of lung cancer cells to cisplatin.
肺癌是最恶性的癌症，在全球范围内发病率和死亡率最高。由于耐药性，目前肺癌的化疗效果不佳，治疗效果差。雷公藤内酯醇（T4）是从雷公藤植物中提取的天然产物，具有强大的免疫抑制和抗肿瘤作用，可能成为肺癌的潜在治疗药物。因此，本研究旨在探讨 T4 降低肺癌细胞化疗耐药性的作用及其机制。1. 分别用 AEG-1 过表达和 AEG-1 敲低质粒转染 A549 和 A549/DDP 细胞。将 A549/DDP 细胞分为 A549/DDP 空质粒组、T4 组和 T4+AEG-1 过表达组。采用 CCK-8 法检测各组细胞的增殖情况。采用 RT-qPCR 和 Western blot 检测 AEG-1 和 MDR-1 的表达。A549 和 A549/DDP 细胞中 AEG-1 的表达与顺铂耐药性呈正相关。当 A549 细胞中 AEG-1 蛋白过表达时，顺铂对 A549 细胞的致死作用减弱（均 P<0.05）。当 A549/DDP 细胞中 AEG-1 蛋白敲低时，顺铂的致死作用明显增强，与相应的对照组细胞相比（均 P<0.05）。随着 A549 和 A549/DDP 细胞中 T4 浓度的增加，AEG-1 蛋白表达逐渐降低。加入 T4 后，A549/DDP 细胞对顺铂的耐药性降低（P<0.05），转染 AEG-1 敲低质粒后，这种作用增强。T4 对增加肺癌细胞对顺铂的敏感性起重要作用。
