胰腺星状细胞通过白细胞介素-22影响胰腺癌侵袭转移及化疗耐药的研究  

Effects of pancreatic stellate cells on malignant progression and chemoresistance of pancreatic cancer by interleukin-22

作　　者：王铁宁 王永红 刘娇 赵建国[2] Wang Tiening;Wang Yonghong;Liu Jiao;Zhao Jianguo(Graduate School of Inner Mongolia Medical University,Hohhot 010110,China;Department of Hepatobiliary Surgery,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010150,China)

机构地区：[1]内蒙古医科大学研究生院,呼和浩特010110 [2]内蒙古医科大学附属医院肝胆胰脾外科,呼和浩特010150

出　　处：《中华实验外科杂志》2023年第1期22-26,共5页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(82060432);内蒙古自治区科技攻关计划基金资助项目(2019GG085);内蒙古自治区自然科学基金资助项目(2019MS08025)。

摘　　要：目的探讨具有不同白细胞介素-22(IL-22)表达水平的胰腺星状细胞(PSC)对胰腺癌细胞侵袭转移及化疗耐药的影响。方法将人原代胰腺癌间质PSC细胞与胰腺癌PANC-1细胞共培养后检测IL-22的表达及胰腺癌细胞的生长增殖能力、迁移和侵袭能力变化;构建稳定敲低或者过表达IL-22的人原代胰腺癌间质PSC细胞并与胰腺癌PANC-1细胞进行体外共培养,检测PANC-1细胞的生长增殖、迁移和侵袭能力;利用稳定敲低或者过表达IL-22的人原代胰腺癌间质PSC细胞并与胰腺癌PANC-1细胞进行体外共培养后检测E-钙黏蛋白(E-cadherin)和波形蛋白(Vimentin)的表达情况;将含有不同表达水平的胰腺癌间质PSC细胞与胰腺癌PANC-1细胞体外共培养并加入不同浓度梯度的吉他西滨培养72 h后检测细胞存活率,计算细胞耐受吉他西滨的半数抑制浓度(IC_(50));将稳定敲低或者过表达IL-22的人原代胰腺癌间质PSC细胞并与胰腺癌PANC-1细胞进行混合后种植于裸鼠皮下,40 d后处理裸鼠取出肿瘤并绘制肿瘤生长曲线,比较两组细胞的成瘤能力。采用t检验分析各组间差异的显著性。结果单纯PANC-1培养组IL-22表达水平(0.907±0.025)明显低于PANC-1与PSC共培养组(4.167±0.306),差异有统计学意义(t=18.420,P<0.05)。细胞增殖实验中过表达组细胞吸光度值(0.727±0.040)明显高于空载对照组(0.563±0.055),差异有统计学意义(t=4.141,P<0.05);敲低组细胞吸光度值(0.327±0.038)明显低于空载对照组(0.530±0.020),差异有统计学意义(t=8.225,P<0.05)。体内成瘤实验中过表达组细胞在裸鼠内成瘤体积[(2711.000±24.880)mm^(3)]明显高于空载对照组[(2037.00±25.514)mm^(3)],差异有统计学意义(t=32.758,P<0.05);敲低组细胞成瘤体积[(636.667±33.501)mm^(3)]明显低于空载对照组[(1959.667±50.053)mm^(3)],差异有统计学意义(t=38.046,P<0.05)。Transwell迁移实验中过表达组细胞计数[(375.667±9.451)个/视野]明显高�Objective Interleukin-22(IL-22)is highly expressed in human primary pancreatic cancer mesenchymal pancreatic stellate cells(PSCs).This study aims to investigate the effects of different expression levels of IL-22 on the invasion and metastasis of pancreatic cancer cells and chemotherapy resistance.Methods The interstitial PSCs of primary pancreatic cancer were co-cultured with PANC-1 cells to detect the expression of IL-22 and the changes of growth,proliferation,migration and invasion ability of pancreatic cancer cells.Human primary pancreatic cancer mesenchymal PSCs with stable knockdown or overexpression of IL-22 were constructed and co-cultured with pancreatic cancer PANC-1 cells in vitro to detect the growth,proliferation,migration and invasion of PANC-1 cells.The expression of E-cadherin and Vimentin in human primary pancreatic cancer mesenchymal PSCs with stable knockdown or overexpression of IL-22 was detected by in vitro co-culture with pancreatic cancer PANC-1 cells.Pancreatic cancer mesenchymal PSCs with different expression levels were co-cultured with pancreatic cancer PANC-1 cells and cultured with guitar sibin of different concentration gradients for 72 h.The survival rate of the cells was detected,and the half maximal inhibitory concentration(IC_(50))of the cells tolerant to guitar sibin was calculated.Human primary pancreatic cancer mesenchymal PSCs with stable knockout or overexpression of IL-22 were mixed with pancreatic cancer PANC-1 cells and implanted subcutaneously in nude mice.After 40 days of treatment,tumors were removed from nude mice and tumor growth curves were drawn to compare the tumor-forming ability of the two groups of cells.T test was used to analyze the significance of differences among the groups.P<0.05 was considered statistically significant.Results The expression level of IL-22 in PANC-1 culture group(0.907±0.025)was significantly lower than that in PANC-1 and PSCs co-culture group(4.167±0.306),and the difference was statistically significant(t=18.420,P<0.05).In cell proli

关 键 词：胰腺星状细胞 白细胞介素-22 胰腺癌 化疗耐药 

分 类 号：R735.9[医药卫生—肿瘤]