Department of Anesthesiology, Huaihe Hospital of Henan University, No. 8, Baobei Road, Gulou District, Kaifeng, 475000, China.
Mol Cell Biochem. 2019 Jun;456(1-2):63-72. doi: 10.1007/s11010-018-3490-x. Epub 2019 Jan 14.
Lidocaine (Lido) is a commonly used local anesthetic, which has been reported in various types of cells. However, the effects of Lido on lung cancer cells remain not understood. The study aimed to investigate the underlying mechanisms of Lido in the cisplatin resistance of A549/DDP cells. Different concentrations of cisplatin (0-320 µM) were used to stimulate A549 and A549/DDP cells, and cell viability and apoptosis were examined. To investigate the effect of Lido on A549/DDP cells, the optimum concentration of Lido was selected to treat A549/DDP cells, and cell viability, apoptosis, migration and invasion were then detected. The relative expression of miR-21 in A549/DDP cells or in Lido-treated A549/DDP cells was analyzed by RT-qPCR. MiR-21 mimic, inhibitor and its control were transfected into A549/DDP cells to explore the regulatory effect of miR-21 on the cisplatin resistance in A549 or A549/DDP cells. The effects of miR-21 on PTEN/PI3K/AKT and PDCD4/JNK pathways were detected by western blot. The cisplatin resistance of A549/DDP cells was higher than that of A549 cells. Lido significantly suppressed cell viability, induced apoptosis, and inhibited cell migration and invasion in A549/DDP cells. Additionally, miR-21 expression in A549/DDP was higher than that in A549 cells, and Lido significantly down-regulated miR-21 expression in A549/DDP cells. MmiR-21 inhibition exhibited the same effects as Lido on the cisplatin resistance of A549/DDP cells. Further, miR-21 suppression regulated PTEN/PI3K/AKT and PDCD4/JNK pathways in A549/DDP cells. These findings indicated that Lido alleviated the cytotoxicity resistance of A549/DDP cells via down-regulation of miR-21.
利多卡因(Lido)是一种常用的局部麻醉剂,已在各种类型的细胞中报道。然而,利多卡因对肺癌细胞的影响尚不清楚。本研究旨在探讨利多卡因在 A549/DDP 细胞顺铂耐药中的潜在机制。用不同浓度的顺铂(0-320 μM)刺激 A549 和 A549/DDP 细胞,检测细胞活力和细胞凋亡。为了研究利多卡因对 A549/DDP 细胞的影响,选择利多卡因的最佳浓度处理 A549/DDP 细胞,然后检测细胞活力、细胞凋亡、迁移和侵袭。通过 RT-qPCR 分析 A549/DDP 细胞或利多卡因处理的 A549/DDP 细胞中 miR-21 的相对表达。将 miR-21 模拟物、抑制剂及其对照转染到 A549/DDP 细胞中,以探讨 miR-21 对 A549 或 A549/DDP 细胞顺铂耐药的调节作用。通过 Western blot 检测 miR-21 对 PTEN/PI3K/AKT 和 PDCD4/JNK 通路的影响。A549/DDP 细胞的顺铂耐药性高于 A549 细胞。利多卡因显著抑制 A549/DDP 细胞的活力,诱导细胞凋亡,并抑制细胞迁移和侵袭。此外,A549/DDP 细胞中的 miR-21 表达高于 A549 细胞,利多卡因显著下调 A549/DDP 细胞中的 miR-21 表达。miR-21 抑制与利多卡因对 A549/DDP 细胞顺铂耐药性的作用相同。此外,miR-21 抑制调节 A549/DDP 细胞中的 PTEN/PI3K/AKT 和 PDCD4/JNK 通路。这些发现表明,利多卡因通过下调 miR-21 减轻了 A549/DDP 细胞的细胞毒性耐药性。