利多卡因对脑胶质瘤细胞恶性生物学行为的影响

刘焰; 李国妍; 陈超

PDF(6470 KB)

湖南师范大学学报医学版 ›› 2024, Vol. 21 ›› Issue (3) : 16-21.

基础医学

利多卡因对脑胶质瘤细胞恶性生物学行为的影响

刘焰, 李国妍, 陈超

作者信息 +

Effect of lidocaine on the malignant biological behavior of glioma cells

LIU Yan, LI Guoyan, CHEN Chao

Author information +

文章历史 +

摘要

目的: 确定利多卡因在体外对脑胶质瘤的作用,并探讨其作用机制。方法: 采用噻唑蓝法、集落形成和Transwell实验分别分析脑胶质瘤细胞细胞增殖、迁移和侵袭,以研究利多卡因对脑胶质瘤进展的影响。通过蛋白质免疫印迹法分析CD133和胶质纤维酸性蛋白（glial fibrillary acidic protein,GFAP）的表达以评估细胞分化。通过蛋白质免疫印迹法分析E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）的表达以评估细胞转移。通过蛋白质免疫印迹法分析音猬因子（sonic hedgehog,SHH）/GLI 家族锌指 1（zinc finger protein GLI1,GLI）信号通路的活性。结果: 与对照组相比,利多卡因在体外抑制脑胶质瘤细胞的增殖、迁移、侵袭和诱导分化,并且降低SHH和GLI的蛋白表达。SHH/GLI信号通路激动剂（SAG）处理部分抑制了利多卡因的功能。结论: 利多卡因通过阻滞SHH/GLI信号通路活性,进而抑制脑胶质瘤的恶性进展。

Abstract

Objective To determine the effect of lidocaine on glioma in vitro and to investigate its mechanism. Methods The effects of lidocaine on glioma progression were investigated by methyl thiazolyl tetrazolium (MTT) assay, colony formation assay and Transwell assay. The expressions of CD133 and glial fibrillary acidic protein (GFAP) were analyzed by Western blotting to evaluate cell differentiation. The expressions of E-cadherin and N-cadherin were analyzed by Western blotting to evaluate cell metastasis. The activity of Sonic Hedgehog (SHH) /glial fibrillary acidic protein (GLI) family zinc finger 1(GLI) signaling pathway was analyzed by Western blotting. Results Lidocaine inhibited the proliferation, migration, invasion and differentiation induction of glioma cells in vitro, and decreased the protein expression of SHH and GLI, which was partially inhibited by SHH/GLI signaling pathway agonist (SAG) treatment. Conclusion Lidocaine inhibits the malignant progression of glioma by blocking the activity of SHH/GLI signaling pathway.

导出引用

刘焰, 李国妍, 陈超. 利多卡因对脑胶质瘤细胞恶性生物学行为的影响[J]. 湖南师范大学学报医学版. 2024, 21(3): 16-21

LIU Yan, LI Guoyan, CHEN Chao. Effect of lidocaine on the malignant biological behavior of glioma cells[J]. Journal of Hunan Normal University(Medical Science). 2024, 21(3): 16-21

中图分类号： R739.4 R363

参考文献

[1] 刘娟, 刘洋, 刘小华, 等. 预后营养指数及其他临床指标与脑胶质瘤术后患者预后的相关性分析 [J]. 实用临床医药杂志, 2023, 27(08): 118-122+125.
[2] MA CC, XIONG Z, ZHU GN, et al.Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a[J]. J Exp Clin Cancer Res, 2016, 35(1): 90.
[3] 何燕, 张建友, 孙建宏. 利多卡因联合阿托品对全麻下择期手术的老年患者心率变异性的影响[J]. 实用临床医药杂志, 2020, 24(18): 54-57.
[4] ADLER DMT, DAMBORG P, VERWILGHEN DR.The antimicrobial activity of bupivacaine, lidocaine and mepivacaine against equine pathogens: An investigation of 40 bacterial isolates[J]. Vet J, 2017, 223: 27-31.
[5] CARACAS HC, MACIEL JV, MARTINS PM, et al.The use of lidocaine as an anti-inflammatory substance: a systematic review[J]. J Dent, 2009, 37(2): 93-97.
[6] D'AGOSTINO G, SAPORITO A, CECCHINATO V, et al. Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration[J]. Br J Anaesth, 2018, 121(4): 962-968.
[7] RUIZ I ALTABA A, PALMA V, DAHMANE N. Hedgehog-Gli signalling and the growth of the brain[J]. Nat Rev Neurosci, 2002, 3(1): 24-33.
[8] BECHER OJ, HAMBARDZUMYAN D, FOMCHENKO EI, et al.Gli activity correlates with tumor grade in platelet-derived growth factor-induced gliomas[J]. Cancer Res, 2008, 68(7): 2241-2249.
[9] EHTESHAM M, SARANGI A, VALADEZ JG, et al.Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells[J]. Oncogene, 2007, 26(39): 5752-5761.
[10] TU Y, NIU M, XIE P, et al.Smoothened is a poor prognosis factor and a potential therapeutic target in glioma[J]. Sci Rep, 2017, 7: 42630.
[11] VOLNITSKIY A, SHTAM T, BURDAKOV V, et al.Abnormal activity of transcription factors gli in high-grade gliomas[J]. PLoS One, 2019, 14(2): e0211980.
[12] WANG K, PAN L, CHE X, et al.Sonic Hedgehog/GLI (1) signaling pathway inhibition restricts cell migration and invasion in human gliomas[J]. Neurol Res, 2010, 32(9): 975-980.
[13] GONG W, ZHAO W, LIU G, et al.Curcumin analogue BDDD-721 exhibits more potent anticancer effects than curcumin on medulloblastoma by targeting Shh/Gli1 signaling pathway[J]. Aging (Albany NY), 2022, 14(13): 5464-5477.
[14] VILLARINHO NJ, VASCONCELOS FDC, MAZZOCCOLI L, et al.Effects of long-term exposure to MST-312 on lung cancer cells tumorigenesis: Role of SHH/GLI-1 axis[J]. Cell Biol Int, 2022, 46(9): 1468-1479.
[15] SAMPETREAN O, SAYA H.Modeling phenotypes of malignant gliomas[J]. Cancer Sci, 2018, 109(1): 6-14.
[16] NAKADA M, NAKADA S, DEMUTH T, et al.Molecular targets of glioma invasion[J]. Cell Mol Life Sci, 2007, 64(4): 458-478.
[17] LI G, QIN Z, CHEN Z, et al.Tumor Microenvironment in Treatment of Glioma[J]. Open Med (Wars), 2017, 12: 247-251.
[18] MOSTOVENKO E, VEGVARI A, REZELI M, et al.Large Scale Identification of Variant Proteins in Glioma Stem Cells[J]. ACS Chem Neurosci, 2018, 9(1): 73-79.
[19] LENG T, LIN S, XIONG Z, et al.Lidocaine suppresses glioma cell proliferation by inhibiting TRPM7 channels[J]. Int J Physiol Pathophysiol Pharmacol, 2017, 9(2): 8-15.
[20] IZDEBSKA M, HALAS-WISNIEWSKA M, ZIELINSKA W, et al.Lidocaine induces protective autophagy in rat C6 glioma cell line[J]. Int J Oncol, 2019, 54(3): 1099-1111.
[21] LU J, JU YT, LI C, et al.Effect of TRPV1 combined with lidocaine on cell state and apoptosis of U87-MG glioma cell lines[J]. Asian Pac J Trop Med, 2016, 9(3): 288-292.
[22] WANG H, WANG D, SHEN Y, et al.GAS5 attenuates the malignant progression of glioma stem-like cells by promoting E-cadherin[J]. Cancer Gene Ther, 2023, 30(3): 450-461.
[23] WANG Y, ZHANG Y, SANG B, et al.Human giant larvae-1 promotes migration and invasion of malignant glioma cells by regulating N-cadherin[J]. Oncol Lett, 2021, 21(2): 167.
[24] LIU A, YU Q, PENG Z, et al.miR-200b inhibits CD133(+) glioma cells by targeting the AKT pathway[J]. Oncol Lett, 2017, 13(6): 4701-4707.
[25] TAMURA K, AOYAGI M, ANDO N, et al.Expansion of CD133-positive glioma cells in recurrent de novo glioblastomas after radiotherapy and chemotherapy[J]. J Neurosurg, 2013, 119(5): 1145-1155.
[26] HU J, SHI B, LIU X, et al.The activation of Toll-like receptor 4 reverses tumor differentiation in human glioma U251 cells via Notch pathway[J]. Int Immunopharmacol, 2018, 64: 33-41.
[27] DOHENY D, MANORE SG, WONG GL, et al.Hedgehog Signaling and Truncated GLI1 in Cancer[J]. Cells, 2020, 9(9): 2144.
[28] KATOH Y, KATOH M.Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation[J]. Curr Mol Med, 2009, 9(7): 873-886.
[29] DONG GZ, JEONG JH, LEE YI, et al.Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway[J]. Arch Pharm Res, 2017, 40(4): 509-517.