毛兰素通过cGAS-STING通路介导的免疫调控机制对胰腺癌发生发展的影响  

Impact of erianin on occurrence and development of pancreatic cancer through cGAS-STING pathway mediated immune regulation mechanism

作　　者：陈巍 韩峥 黄莎莎 蔡一珊 郭芳 田霞 CHEN Wei;HAN Zheng;HUANG Sha-sha;CAI Yi-shan;GUO Fang;TIAN Xia(Department of Gastroenterology,the Third Hospital of Wuhan,Wuhan HUBEI 430060,China)

机构地区：[1]武汉市第三医院消化内科,湖北武汉430060

出　　处：《中国新药与临床杂志》2024年第10期790-795,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：湖北省卫生健康委员会科研项目(WJ2023M129)。

摘　　要：目的探讨毛兰素调节环GMP-AMP合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路对胰腺癌发生发展的影响。方法将人胰腺癌细胞系SW1990细胞分为对照组,毛兰素低、中、高浓度(10、20、40 nmol·L^(-1))组,RU.521(cGAS抑制剂,1μmol·L^(-1))组,毛兰素(40 nmol·L^(-1))+RU.521(1μmol·L-1)组。CCK-8法检测SW1990细胞增殖,流式细胞术检测细胞凋亡,划痕实验和Transwell实验检测细胞迁移和侵袭,Western blot法检测细胞周期蛋白D1(cyclin D1)、Bcl-2相关X蛋白(Bax)、基质金属蛋白酶(MMP)-2、MMP-9、cGAS和STING蛋白表达。SW1990细胞与自然杀伤(NK)细胞共培养48 h,ELISA法检测共培养上清中颗粒酶B(granzyme B)、穿孔素(PF)水平,检测NK细胞杀伤活力变化。结果与对照组比较,毛兰素低、中、高浓度组细胞增殖率、划痕愈合率和侵袭细胞数目减少,cyclin D1、MMP-2、MMP-9蛋白表达降低,细胞凋亡率升高,Bax、cGAS、STING蛋白表达降低,呈浓度依赖性(P<0.05);而RU.521组上述指标变化趋势相反(P<0.05)。与毛兰素高浓度组相比,毛兰素+RU.521组细胞增殖率、划痕愈合率和侵袭细胞数目及cyclin D1、MMP-2、MMP-9、Bax、cGAS、STING蛋白表达增高,细胞凋亡率降低(P<0.05)。共培养实验中,与对照组比较,毛兰素低、中、高浓度组细胞上清中granzyme B、PF水平和NK细胞杀伤活力升高,且呈浓度依赖性(P<0.05),而RU.521组对应指标变化趋势相反(P<0.05);与毛兰素高浓度组相比,毛兰素+RU.521组granzyme B、PF水平和NK细胞杀伤活力降低(P<0.05)。结论毛兰素可能通过激活cGAS-STING信号通路抑制胰腺癌细胞的增殖、迁移、侵袭及免疫逃逸,促进细胞凋亡。AIM To investigate the impact of erianin on the development of pancreatic cancer by regulating cyclic GMP-AMP synthase-stimulator of interferon gene(cGAS-STING)signal pathway.METHODS SW1990 cells were divided into control group,low-,medium-and high-concentration erianin groups(10,20,40 nmol·L^(-1)),RU.521(cGAS inhibitor)group(1μmol·L^(-1)),and erianin(40 nmol·L^(-1))+RU.521(1μmol·L^(-1))group.The proliferation was detected by CCK-8 method,and apoptosis was detected by flow cytometry.The migration and invasion of SW1990 cells were detected by scratch test and Transwell test,respectively.Western blot was applied to detect the protein expressions of cyclin D1,Bcl-2 associated X protein(Bax),matrix metalloproteinase(MMP)-2,MMP-9,cGAS and STING in SW1990 cells.SW1990 cells were co-cultured with NK cells for 48 hours,the levels of granzyme B and perforin(PF)in co-culture supernatant were detected by ELISA,and NK cell killing activity was detected.RESULTS Compared with the control group,the cell proliferation rate,the rate of scratch healing,the number of invasive cells were decreased in the low-,medium-and high-concentration erianin groups,the protein expressions of cyclin D1,MMP-2,MMP-9 were decreased,the apoptosis rate was increased,and the protein expressions of Bax,cGAS and STING were decreased in a concentration-dependent manner(P<0.05),while the change trends of the above indexes in the RU.521 group were opposite(P<0.05).Compared with the high-concentration erianin group,the cell proliferation rate,scratch healing rate,the number of invasive cells,and the protein expressions of cyclin D1,MMP-2,MMP-9,Bax,cGAS and STING in the erianin+RU.521 group were increased,and the apoptosis rate was decreased(P<0.05).In the co-culture experiment,compared with the control group,the levels of granzyme B and PF and NK cell killing activity in the cell supernatant of the low-,medium-and high-concentration erianin groups were increased in a concentrationdependent manner(P<0.05),while the change trends of corresponding indexe

关 键 词：毛兰素 胰腺肿瘤 细胞增殖 细胞迁移抑制 环GMP 

分 类 号：R735.9[医药卫生—肿瘤]