Department of Pharmacology, College of Pharmacy, P. R. China.
Biotechnological Institute of Chinese Materia Medica, Jinan University, Guangzhou 510632, P. R. China.
Am J Chin Med. 2022;50(7):1963-1992. doi: 10.1142/S0192415X22500847. Epub 2022 Aug 31.
Cisplatin (DDP)-based chemotherapy is the first-line regimen for advanced non-small cell lung cancer (NSCLC) patients. However, advanced NSCLC patients may have innate resistance to DDP or develop resistance during DDP treatment. We investigated a natural compound, arteannuin B (Art B), for its potential effects on DDP resistance in NSCLC. Art B was isolated from by chromatographic purification and spectral elucidation. The activities of Art B on DDP-mediated effects were examined using and assays. We observed significant correlations in T stage, clinical stage, chemotherapy resistance and poor survival of NSCLC patients with low Cx43 expression. Art B enhanced the effectiveness of cisplatin by increasing Cx43 expression in normal and DDP-resistant NSCLC cells. Art B also increased DDP uptake through up-regulating Cx43. The combination of DDP and Art B showed better therapeutic effect than individual treatments both and . Art B increased intracellular Fe[Formula: see text] level, promoted calcium influx, and activated gap junction and MAPK pathways, which might contribute to Art B-mediated effects. Art B may serve as a new drug candidate to enhance the antitumor effect of DDP on NSCLC.
顺铂（DDP）为基础的化疗是晚期非小细胞肺癌（NSCLC）患者的一线治疗方案。然而，晚期 NSCLC 患者可能对 DDP 具有先天耐药性，或在 DDP 治疗过程中产生耐药性。我们研究了一种天然化合物，青蒿素 B（Art B），以评估其对 NSCLC 中 DDP 耐药性的潜在影响。Art B 通过色谱纯化和光谱阐明从青蒿中分离出来。使用划痕和侵袭实验检测 Art B 对 DDP 介导的作用的影响。我们观察到，在 NSCLC 患者中，Cx43 低表达与 T 分期、临床分期、化疗耐药和不良生存相关。Art B 通过增加正常和 DDP 耐药 NSCLC 细胞中的 Cx43 表达，增强了顺铂的疗效。Art B 还通过上调 Cx43 增加了 DDP 的摄取。DDP 和 Art B 的联合治疗比单独治疗具有更好的治疗效果，无论是划痕实验还是侵袭实验。Art B 增加了细胞内 Fe[Formula: see text]水平，促进了钙内流，并激活了缝隙连接和 MAPK 通路，这可能是 Art B 介导作用的原因。Art B 可能成为一种新的药物候选物，以增强 DDP 对 NSCLC 的抗肿瘤作用。
