利多卡因抑制RhoA/ROCK通路对食管癌细胞增殖侵袭血管生成拟态的影响

doi:10.3969/j.issn.1006-6233.2025.09.07

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摘要 目的: 探讨利多卡因抑制小GTP酶(RhoA)/Rho相关的蛋白激酶(ROCK)通路对食管癌(EC)细胞增殖、侵袭、血管生成拟态的影响。方法: 体外培养人EC细胞系Eca-109,将其分为NC组、利多卡因低剂量组(利多卡因5mmoL/L)、利多卡因中剂量组(利多卡因10mmoL/L)、利多卡因高剂量组(利多卡因15mmoL/L)、利多卡因高剂量+RhoA/ROCK通路激活剂(LPA)组(15mmoL/L利多卡因+50μmoL/L LPA),分别采用克隆形成实验、Transwell小室实验、Matrigel管腔形成实验检测各组Eca-109细胞增殖、侵袭能力及血管生成;qRT-PCR实验检测各组Eca-109细胞中RhoA和ROCK mRNA表达量;Western blot检测各组Eca-109细胞中RhoA、ROCK、CCND1、Myc、VEGF、TIMP-1蛋白表达量。结果: 与NC组相比,利多卡因低、中、高剂量组Eca-109细胞集落形成数量、侵袭数量、血管生成管状结构数量均减少,RhoA、ROCK mRNA及其蛋白表达量降低,CCND1、Myc、VEGF蛋白表达量也明显下降,TIMP-1蛋白表达量明显上升(P<0.05);与利多卡因高剂量组相比,利多卡因高剂量+LPA组Eca-109细胞集落形成数量、侵袭数量、血管生成管状结构数量增加,RhoA、ROCK mRNA及其蛋白表达量升高,CCND1、Myc、VEGF蛋白表达量也明显上升,TIMP-1蛋白表达量明显下降(P<0.05)。结论: 利多卡因可通过抑制RhoA/ROCK通路抑制EC细胞增殖、侵袭以及血管生成拟态。

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	尼特伟布子
	陈勇
	张玉锋
	周平

关键词 ：食管癌, 利多卡因, RhoA/ROCK通路, 增殖, 侵袭, 血管生成拟态

Abstract：Objective: To explore the effects of lidocaine on the proliferation, invasion, and vascular mimicry of esophageal cancer (EC) cells by inhibiting the small GTPase (RhoA)/Rho-associated coiled-coil containing protein kinase (ROCK) pathway. Methods: The human EC cell line Eca-109 was cultured in vitro and assigned into NC group, low-dose lidocaine group (lidocaine 5 mmol/L), medium dose lidocaine group (lidocaine 10mmol/L), high-dose lidocaine group (lidocaine 15 mmol/L), and high-dose lidocaine+RhoA/ROCK pathway activator (LPA) group (lidocaine 15 mmol/L+50μmol/L LPA). The clone formation experiment, Transwell chamber experiment, and Matrigel lumen formation experiment were used to detect the proliferation and invasion abilities, and angiogenesis of Eca-109 cells in each group. The qRT-PCR experiment was used to detect the RhoA and ROCK mRNA of Eca-109 cells in each group. Western blot was used to detect the RhoA, ROCK, CCND1, Myc, VEGF, and TIMP-1 proteins of Eca-109 cells. Results: Compared with the NC group, the low, medium, and high dose lidocaine groups showed a decrease in the numbers of Eca-109 cell colony formation, invasion, and angiogenesis tubular structures, reduced RhoA, ROCK mRNA, and their proteins, and prominently decreased CCND1, Myc, and VEGF proteins, and prominently increased TIMP-1 protein (P<0.05). Compared with the high-dose lidocaine group, the high-dose lidocaine+LPA group showed an increase in the numbers of Eca-109 cell colony formation, invasion, and angiogenesis tubular structures, increased RhoA, ROCK mRNA, and their proteins, and prominently increased CCND1, Myc, and VEGF proteins, and prominently reduced TIMP-1 protein (P<0.05). Conclusion: Lidocaine can inhibit proliferation, invasion, and vasculogenic mimicry of EC cells by suppressing RhoA/ROCK pathway.

Key words： Esophageal cancer Lidocaine RhoA/ROCK pathway Proliferation Invasion Vasculogenic mimicry

基金资助:四川省医学科技创新科学研究项目,(编号:YCH-KY-YCZD2024-147)

引用本文:

尼特伟布子, 陈勇, 张玉锋, 周平. 利多卡因抑制RhoA/ROCK通路对食管癌细胞增殖侵袭血管生成拟态的影响[J]. 河北医学, 2025, 31(9): 1446-1452.
NITeweibuzi, CHEN Yong, ZHANG Yufeng, et al. Effects of Lidocaine on the Proliferation Invasion and Vascular Mimicry of Esophageal Cancer Cells by Inhibiting the RhoA/ROCK Pathway. HeBei Med, 2025, 31(9): 1446-1452.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.09.07 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I9/1446

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