首页|利多卡因调节RhoA/ROCK轴对结直肠癌细胞生物学行为的影响

利多卡因调节RhoA/ROCK轴对结直肠癌细胞生物学行为的影响

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该文主要探讨利多卡因(lidocaine,Lido)通过调节Ras同源基因家族成员A(RhoA)/Rho相关的卷曲螺旋激酶(ROCK)轴对结直肠癌(CRC)细胞生物学行为的影响.该研究使用0~1 250 μmol/L的利多卡因处理人结直肠癌细胞LS513,CCK-8法检测细胞活力筛选适宜药物浓度.将细胞分为对照组(Control组)、利多卡因低浓度组(Lido-L组,500 μmol/L Lido)、利多卡因中浓度组(Lido-M组,750 μmol/L Lido)、利多卡因高浓度组(Lido-H组,1 000 μmol/L Lido)和利多卡因高浓度+ROCK信号通路激活剂LPA组(Lido-H+LPA组,1 000 μmol/L Lido+10 μmol/LLPA).Edu检测细胞增殖;划痕愈合实验和Transwell小室实验分别检测细胞迁移和侵袭能力;流式细胞仪检测细胞凋亡情况;Western blot检测 PCNA、Bax、Bcl-2、RhoA、ROCK 1、E-cadherin和N-cadherin蛋白表达情况.该研究得出与0 μmol/L利多卡因相比,500 μmol/L、750 μmol/L、1 000μmol/L和 1 250 μmol/L利多卡因处理的LS513细胞活力显著降低(P<0.05),选择500 μmol/L、750 μmol/L和1 000 μmol/L的利多卡因进行后续实验.与Control组相比,Lido-L组、Lido-M组和Lido-H组LS513细胞Edu阳性率,划痕愈合率,细胞侵袭数及PCNA、N-cadherin、Bcl-2、RhoA和ROCK 1蛋白表达水平降低(P<0.05),细胞凋亡率以及E-cadherin和Bax蛋白表达增加(P<0.05);与Lido-H组相比,Lido-H+LPA组LS513细胞Edu阳性率,划痕愈合率,细胞侵袭数及PCNA、N-cadherin,Bcl-2,RhoA和ROCK 1蛋白表达水平显著增加(P<0.05),细胞凋亡率、E-cadherin和Bax蛋白表达水平显著降低(P<0.05).利多卡因可能通过抑制RhoA/ROCK信号通路抑制结直肠癌细胞恶性生物学行为.
Effect of Lidocaine Regulating RhoA/ROCK Axis on Biological Behavior of Colorectal Cancer Cells
This study focused on the effects of Lido(lidocaine)on the biological behavior of CRC(colorectal cancer)cells by regulating the RhoA(Ras homologous gene family member A)/ROCK(Rho associated coiled-coil forming protein kinase)axis.In this study,human colorectal cancer cells LS513 were treated with 0~1 250 μmol/L lidocaine,and cell viability was detected by CCK-8 method to screen suitable drug concentration.The cells were grouped into Control group,lidocaine low concentration group(Lido-L group,500 μmol/L Lido),lidocaine medium concentration group(Lido-M group,750 μmol/L Lido),lidocaine high concentration group(Lido-H group,1 000 μmol/L Lido)and lidocaine high concentration+ROCK signal pathway activator LPA group(Lido-H+LPA group,1 000 μmol/L Lido+10 μmol/L LPA group).Edu was applied to detect cell proliferation;scratch heal-ing test and transwell chamber test were applied to detect cell migration and invasion ability,respectively;flow cy-tometry was applied to detect cell apoptosis;Western blot was applied to detect the expression of PCNA,Bax,Bcl-2,RhoA,ROCK 1,E-cadherin,and N-cadherin proteins.In this study,compared with 0 μmol/L Lido,the activity of LS513 cells treated with 500 μmol/L,750 μmol/L,1 000 μmol/L and 1 250 μmol/L Lido obviously decreased(P<0.05),lidocaine of 500 μmol/L,750 μmol/L and 1 000 μmol/L was selected for subsequent experiments.Compared with the Control group,the Edu positive rate,scratch healing rate,cell invasion number,and PCNA,N-cadherin,Bcl-2,RhoA,and ROCK 1 protein expression of LS513 cells in the Lido-L group,Lido-M group,and Lido-H group decreased sequentially(P<0.05),the apoptosis rate,E-cadherin and Bax protein expression increased sequentially(P<0.05);compared with the Lido-H group,the Edu positive rate,scratch healing rate,cell invasion number,and PCNA,N-cadherin,Bcl-2,RhoA,and ROCK 1 protein expression of LS513 cells in the Lido-H+LPA group obviously increased(P<0.05),the apoptosis rate,E-cadherin,and Bax protein expression were obviously reduced(P<0.05).Lidocaine may inhibit the malignant biological behavior of colorectal cancer cells by inhibiting RhoA/ROCK signaling pathway.

lidocaineRas homolog gene family member A/Rho associated coiled-coil forming protein ki-nase signal pathwaycolorectal cancermalignant biological behavior

赵馨、尹健、贾彤

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张家口市第五医院麻醉科,张家口 075000

张家口市第一医院麻醉科,张家口 075000

河北北方学院附属第一医院麻醉科,张家口 075000

利多卡因 Ras同源基因家族成员A/Rho相关的卷曲螺旋激酶信号通路 结直肠癌 恶性生物学行为

张家口市市级科技计划(2018)

1821153H

2024

中国细胞生物学学报
中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,中国细胞生物学学会

中国细胞生物学学报

CSTPCD
影响因子:0.554
ISSN:1674-7666
年,卷(期):2024.46(3)
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