Shen Junmei, Han Lina, Xue Yongxian, Li Chao, Jia Huiqun, Zhu Kangsheng
Department of Anesthesiology, The Forth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Blood Transfusion, The Forth Hospital of Hebei Medical University, Shijiazhuang, China.
Front Pharmacol. 2022 Feb 23;12:806954. doi: 10.3389/fphar.2021.806954. eCollection 2021.
Ropivacaine is widely used to induce regional anesthesia during lung cancer surgery. Previous studies reported that amide-linked local anesthetics, e.g., ropivacaine, affected the biological behavior of lung adenocarcinoma cells, but the conclusion is controversial and warrants further study. This study set out to investigate the biological effects of ropivacaine on cultured lung cancer cells and underlying mechanisms. Lung cancer cell lines (A549 and H1299) were cultured and then treated with or without ropivacaine (0.5, 1, and 2 mM) for 48 or 72 h. Their proliferation, migration, and invasion together with cell death and molecules including hypoxia inducible factor (HIF)-1α, VEGF, matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 expression associated with these changes were determined. Ropivacaine significantly inhibited proliferation and migration, invasion, and cell death in a concentration-dependent manner in both cell lines. Ropivacaine also promoted cell death and induced a concentration- and time-dependent cell arrest towards the G0/G1 phase. Expression of VEGF, MMP-1, MMP-2, MMP-9, and HIF-1α in both cell lines was also inhibited by ropivacaine in a concentration-related manner. Our data indicated that ropivacaine inhibited lung cancer cell malignancy, which may be associated with downregulation of cell-survival-associated cellular molecules. The translational value of the current work is subjected to further study.
罗哌卡因被广泛用于肺癌手术中诱导区域麻醉。先前的研究报道，酰胺类局部麻醉药，如罗哌卡因，会影响肺腺癌细胞的生物学行为，但该结论存在争议，值得进一步研究。本研究旨在探讨罗哌卡因对培养的肺癌细胞的生物学效应及其潜在机制。培养肺癌细胞系（A549和H1299），然后用或不用罗哌卡因（0.5、1和2 mM）处理48或72小时。测定它们的增殖、迁移和侵袭以及细胞死亡情况，以及与这些变化相关的包括缺氧诱导因子（HIF）-1α、血管内皮生长因子（VEGF）、基质金属蛋白酶（MMP）-1、MMP-2和MMP-9表达等分子情况。罗哌卡因在两种细胞系中均以浓度依赖性方式显著抑制增殖、迁移、侵袭和细胞死亡。罗哌卡因还促进细胞死亡，并诱导细胞浓度和时间依赖性地停滞于G0/G1期。罗哌卡因还以浓度相关方式抑制两种细胞系中VEGF、MMP-1、MMP-2、MMP-9和HIF-1α的表达。我们的数据表明，罗哌卡因抑制肺癌细胞的恶性程度，这可能与下调细胞存活相关的细胞分子有关。当前工作的转化价值有待进一步研究。
