Department of Anesthesia, Hubei Cancer Hospital, Wuhan, Hubei, China (mainland).
Med Sci Monit. 2020 Mar 30;26:e919786. doi: 10.12659/MSM.919786.
BACKGROUND Cisplatin (cis-diamminedichloroplatinum, DDP) resistance is identified as the primary obstacle during lung cancer treatment, while DDP resistance is exist extensively. This report was to investigate the roles of propofol in lung cancer cells tolerance to DDP and the potential mechanisms. MATERIAL AND METHODS A549 and A549/DDP cells were treated with DDP for 48 hours, and cell proliferation suppression rate was detected by MTT (thiazolyl blue tetrazolium bromide) assay and half maximal inhibitory concentration (IC₅₀) of DDP to lung cancer cells was calculated. Besides, cell proliferation and apoptosis were determined by MTT assay and flow cytometry assay respectively in propofol-treated A549/DDP and A549 cells. Furthermore, we performed MTT assay to determine the influence of propofol on the sensitivity of lung cancer cells to DDP. RESULTS The results demonstrated that the IC₅₀ of DDP to A549 cells was lower than that in A549/DDP cells. Propofol dramatically inhibited cell proliferation and promoted cell apoptosis of A549/DDP and A549 cells. In addition, propofol significantly improved the anti-proliferative impact of DDP in A549/DDP and A549 cells, and the value of IC₅₀ for DDP in the A549/DDP and A549 cells were decreased after propofol treatment compare to the control group. Moreover, propofol inhibited the Wnt/ß-catenin pathway in a dose-dependent manner in both A549/DDP and A549 cells. CONCLUSIONS Our report indicated that propofol could control lung cancer cell proliferation and apoptosis, and stimulated the suppression function of DDP on lung cancer cell multiplication via the Wnt/ß-catenin signaling pathway, and also provided a new treatment for DDP tolerance to cure lung cancer in clinical.
顺铂（cis-diamminedichloroplatinum，DDP）耐药被认为是肺癌治疗过程中的主要障碍，而 DDP 耐药广泛存在。本报告旨在研究异丙酚在肺癌细胞对 DDP 耐药中的作用及其潜在机制。
用 DDP 处理 A549 和 A549/DDP 细胞 48 小时，噻唑蓝（MTT）比色法检测细胞增殖抑制率，计算 DDP 对肺癌细胞的半数抑制浓度（IC₅₀）。此外，用 MTT 法和流式细胞术分别检测异丙酚处理的 A549/DDP 和 A549 细胞的增殖和凋亡。进一步用 MTT 法测定异丙酚对肺癌细胞对 DDP 敏感性的影响。
结果表明，DDP 对 A549 细胞的 IC₅₀ 低于 A549/DDP 细胞。异丙酚显著抑制 A549/DDP 和 A549 细胞的增殖并促进细胞凋亡。此外，异丙酚显著增强了 DDP 对 A549/DDP 和 A549 细胞的增殖抑制作用，与对照组相比，异丙酚处理后 A549/DDP 和 A549 细胞中 DDP 的 IC₅₀ 值降低。此外，异丙酚以剂量依赖的方式抑制 A549/DDP 和 A549 细胞中的 Wnt/ß-catenin 通路。
本报告表明，异丙酚可以控制肺癌细胞的增殖和凋亡，并通过 Wnt/ß-catenin 信号通路刺激 DDP 对肺癌细胞增殖的抑制作用，为临床治疗 DDP 耐药性肺癌提供了新的治疗方法。
