CXC趋化因子配体11/CXC趋化因子受体3生物轴在胆囊癌侵袭转移中的作用及其机制  

Role and mechanism of CXC chemokine ligand 11/CXC chemokine receptor 3 biological axis in the invasion and metastasis of gallbladder cancer

作　　者：曹阳 严秋亮 Cao Yang;Yan Qiuliang(Department of Gastric Surgery,Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital),Hangzhou 310022,China;Department of General Surgery,Fourth Affiliated Hospital,Zhejiang University School of Medicine,Yiwu 322000,China)

机构地区：[1]中国科学院大学附属肿瘤医院(浙江省肿瘤医院)胃外科,杭州310022 [2]浙江大学医学院附属第四医院普外科,义乌322000

出　　处：《中华实验外科杂志》2023年第9期1757-1760,共4页Chinese Journal of Experimental Surgery

基　　金：浙江省自然科学基金(LY21H160036);浙江省医药卫生科技计划项目(2019RC174);金华市重大科学技术研究计划项目(2021-3-001a)。

摘　　要：目的探讨CXC趋化因子配体11(CXCL11)/CXC趋化因子受体3(CXCR3)生物轴对胆囊癌细胞侵袭迁移的调控作用及其机制。方法将胆囊癌细胞株GBC-SD与外源性CXCL11共培养处理后,蛋白质印迹法(Western blot)检测局部黏着斑激酶(FAK)、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(PKB/Akt)的表达及磷酸化水平,Transwell实验检测细胞的侵袭迁移能力。采用RNA干扰技术沉默CXCR3基因表达,观察其对CXCL11介导FAK/PI3K/Akt信号通路活化的影响。评估CXCR3基因敲减、FAK抑制剂PF573228对CXCL11诱导胆囊癌细胞侵袭迁移的影响。组间比较采用独立样本t检验。结果Western blot实验结果表明,CXCL11共培养组磷酸化FAK(p-FAK)、磷酸化PI3K(p-PI3K)、磷酸化Akt(p-Akt)的相对表达量(0.849±0.082、0.824±0.084、0.865±0.081)均显著高于空白对照组(0.186±0.034、0.195±0.038、0.191±0.033),差异有统计学意义(t=12.917、11.821、13.286,P<0.05);CXCR3敲减+CXCL11共培养组p-FAK、p-PI3K、p-Akt的相对表达量(0.215±0.048、0.223±0.057、0.217±0.052)均显著低于CXCL11共培养组(0.849±0.082、0.824±0.084、0.865±0.081),差异有统计学意义(t=11.578、10.234、11.605,P<0.05)。Transwell实验结果显示,CXCL11共培养组细胞的侵袭迁移能力显著高于空白对照组[(168.2±18.4)个比(70.8±9.1)个,t=10.635,P<0.05];CXCR3敲减+CXCL11共培养组细胞的侵袭迁移能力显著低于CXCL11共培养组[(79.6±10.1)个比(168.2±18.4)个,t=9.445,P<0.05];PF573228预处理+CXCL11共培养组细胞的侵袭迁移能力显著低于CXCL11共培养组[(86.4±11.8)个比(168.2±18.4)个,t=8.375,P<0.05]。结论CXCL11/CXCR3生物轴通过激活FAK/PI3K/Akt信号通路促进胆囊癌细胞的侵袭迁移能力。Objective To investigate the regulatory role and mechanism of CXC chemokine ligand 11(CXCL11)/CXC chemokine receptor 3(CXCR3)biological axis in the invasion and migration of gallbladder cancer(GBC)cells.Methods After co-culture of GBC-SD cells with exogenous CXCL11,the expression and phosphorylation levels of focal adhesion kinase(FAK),phosphoinositide 3-kinase(PI3K)and protein kinase B(PKB/Akt)were detected by Western blotting.Transwell assay was also performed to assess the cell invasive and migration ability.RNA interference was employed to silence the expression of CXCR3 gene and then the effect of CXCR3 knockdown on CXCL11-mediated FAK/PI3K/Akt pathway activation was evaluated.We also investigated the effect of CXCR3 knockdown and FAK inhibitor PF573228 on CXCL11-induced cell invasion and migration,respectively.Comparisons between groups were performed by independent sample t-test.Results Western blotting analysis showed that the relative expression levels of phosphorylated FAK(p-FAK),phosphorylated PI3K(p-PI3K)and phosphorylated Akt(p-Akt)(0.849±0.082,0.824±0.084,0.865±0.081)in CXCL11-treated group were significantly higher than those(0.186±0.034,0.195±0.038,0.191±0.033)in the control group,and the differences were statistically significant(t=12.917,11.821,13.286,all P<0.05).The relative expression levels of p-FAK,p-PI3K and p-Akt(0.215±0.048,0.223±0.057,0.217±0.052)in CXCR3 knockdown+CXCL11-treated group were significantly lower than those(0.849±0.082,0.824±0.084,0.865±0.081)in the CXCL11-treated group,and the differences were statistically significant(t=11.578,10.234,11.605,all P<0.05).Transwell assay indicated that the cell invasive and migration ability in CXCL11-treated group significantly increased as compared with that in the control group[(168.2±18.4)cells vs.(70.8±9.1)cells,t=10.635,P<0.05].The cell invasive and migration ability in CXCR3 knockdown+CXCL11-treated group significantly decreased as compared with that in CXCL11-treated group[(79.6±10.1)cells vs.(168.2±18.4)cells,t=9.445

关 键 词：胆囊癌 CXC趋化因子配体11 CXC趋化因子受体3 局部黏着斑激酶 侵袭 转移 

分 类 号：R735.8[医药卫生—肿瘤]