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

Effect of Lidocaine Regulating RhoA/ROCK Axis on Biological Behavior of Colorectal Cancer Cells

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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.
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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