Department of Anesthesiology, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China.
Department of UI Trasonography, Weihaiwei People's Hospital, Weihai, 264200, China.
Dig Dis Sci. 2022 Jun;67(6):2244-2256. doi: 10.1007/s10620-021-07055-6. Epub 2021 May 29.
Lidocaine has been manifested to exert anti-tumor role in gastric cancer (GC) progression. However, the action mechanism by which Lidocaine functions in GC has not been fully elucidated.
The study aimed to reveal the molecular mechanism of Lidocaine in GC progression.
Cell clonogenicity and viability were assessed by colony formation and methyl thiazolyl tetrazolium assays, respectively. Transwell assay was employed to detect cell migration and invasion. Flow cytometry was implemented to monitor cell apoptosis. Relative expression of circular RNA ANO5 (circ_ANO5), microRNA (miR)-21-5p and Leukemia inhibitory factor receptor (LIFR) was examined by quantitative reverse transcription-polymerase chain reaction. Western blot assay was performed to analyze the levels of LIFR and cell metastasis-related proteins. The target relationship between miR-21-5p and circ_ANO5 or LIFR was confirmed by dual-luciferase reporter assay. In addition, xenograft model was established to explore the role of Lidocaine in vivo.
Lidocaine inhibited cell proliferation, migration and invasion, while promoted apoptosis of GC cells. Lidocaine upregulated circ_ANO5 and LIFR expression, but downregulated miR-21-5p expression in GC cells. Additionally, expression of circ_ANO5 and LIFR was decreased, while miR-21-5p expression was increased in GC cells. Circ_ANO5 depletion or miR-21-5p overexpression attenuated Lidocaine-induced anti-proliferative and anti-metastatic effects on GC cells. Circ_ANO5 could sponge miR-21-5p, and miR-21-5p targeted LIFR. Moreover, Lidocaine suppressed the tumor growth in vivo.
Lidocaine might GC cell malignancy by modulating circ_ANO5/miR-21-5p/LIFR axis, highlighting a novel insight for GC treatment.
利多卡因已被证明在胃癌（GC）进展中发挥抗肿瘤作用。然而，利多卡因在 GC 中发挥作用的作用机制尚未完全阐明。
本研究旨在揭示利多卡因在 GC 进展中的分子机制。
通过集落形成和噻唑蓝比色法分别评估细胞集落形成能力和活力。Transwell 检测法用于检测细胞迁移和侵袭。流式细胞术用于监测细胞凋亡。采用定量逆转录聚合酶链反应检测环状 RNA ANO5（circ_ANO5）、微小 RNA（miR）-21-5p 和白血病抑制因子受体（LIFR）的相对表达。Western blot 检测法用于分析 LIFR 和细胞转移相关蛋白的水平。通过双荧光素酶报告基因检测法验证 miR-21-5p 与 circ_ANO5 或 LIFR 的靶关系。此外，还建立了异种移植模型以在体内研究利多卡因的作用。
利多卡因抑制 GC 细胞的增殖、迁移和侵袭，同时促进其凋亡。利多卡因上调 GC 细胞中 circ_ANO5 和 LIFR 的表达，同时下调 miR-21-5p 的表达。此外，GC 细胞中 circ_ANO5 和 LIFR 的表达降低，而 miR-21-5p 的表达增加。circ_ANO5 耗竭或 miR-21-5p 过表达可减弱利多卡因对 GC 细胞的抗增殖和抗转移作用。circ_ANO5 可以与 miR-21-5p 结合，而 miR-21-5p 则靶向 LIFR。此外，利多卡因抑制了体内肿瘤的生长。
利多卡因可能通过调节 circ_ANO5/miR-21-5p/LIFR 轴抑制 GC 细胞的恶性程度，为 GC 的治疗提供了新的思路。
