咖啡因通过FAK/AKT/ROCK通路调控人脑胶质瘤U-373MG细胞的恶性生物学行为  

Caffeine modulates the malignant biological behaviors of human brain glioma U-373MG cells by regulating the FAK/AKT/ROCK pathway

作　　者：徐加志 张芸 陈大刚 高风全 任德帅 吴卫东 杜妍 王娜[2] XU Jiazhi;ZHANG Yun;CHEN Dagang;GAO Fengquan;REN Deshuai;WU Weidong;DU Yan;WANG Na(Department of Neurosurgery,the Third Affiliated Hospital of Qiqihar Medical University,Qiqihar 161000 Heilongjiang,China;Clinical Psychology Teaching and Research Office,Qiqihar Medical College,Qiqihar 161000,Heilongjiang,China)

机构地区：[1]齐齐哈尔医学院附属第三医院神经外科,黑龙江齐齐哈尔161000 [2]齐齐哈尔医学院临床心理学教研室,黑龙江齐齐哈尔161000

出　　处：《中国肿瘤生物治疗杂志》2024年第6期573-578,共6页Chinese Journal of Cancer Biotherapy

基　　金：齐齐哈尔医学科学院临床科研基金项目(No.QMSI2020L-14)。

摘　　要：目的:探讨咖啡因通过调节FAK/AKT/ROCK信号通路来影响人脑胶质瘤U-373MG细胞的增殖、迁移和侵袭能力。方法:常规培养U-373MG细胞,将其分为对照组、咖啡因低剂量(1 mmol/L)组、咖啡因高剂量(2 mmol/L)组、PF573228组(FAK抑制剂,1μmol/L)、咖啡因高剂量+SC79组(AKT激活剂,8mg/L)。用CCK-8法、Transwell小室实验、流式细胞术和WB法分别检测各组U-373MG细胞的增殖、迁移、侵袭及凋亡,以及U-373MG细胞中p-FAK、p-AKT、p-ROCK、Ki67、MMP-9蛋白表达水平。建立U-373MG细胞裸鼠移植瘤模型,观察咖啡因对移植瘤生长的影响,WB法检测移植瘤组织中相关蛋白的表达。结果:咖啡因、PF573228可显著抑制U-373MG细胞的增殖、迁移、侵袭能力,促进U-373MG细胞凋亡,抑制p-FAK、p-AKT、p-ROCK、Ki67、MMP-9蛋白的表达(均P<0.05),SC79则可部分逆转咖啡因对U-373MG细胞的作用(均P<0.05)。咖啡因可显著抑制移植瘤的生长及移植瘤组织中上述相关蛋白的表达(均P<0.05)。结论:咖啡因可通过抑制FAK/AKT/ROCK信号通路抑制U-373MG细胞的增殖、迁移和侵袭能力,并促进其凋亡。Objective:To investigate the effects of caffeine on the proliferation,migration and invasion abilities of human brain glioma U-373MG cells by regulating the FAK/AKT/ROCK signaling pathway.Methods:U-373MG cells were routinely cultured and divided into the control group,the low dose caffeine(1 mmol/L)group,the high dose caffeine(2 mmol/L)group,the PF573228 group(FAK inhibitor,1μmol/L),and the high dose caffeine+SC79 group(AKT activator,8 mg/L).The proliferation ability,migration ability,invasion ability and apoptosis rate of U-373MG cells in each group as well as the expression levels of p-FAK,p-AKT,p-ROCK,Ki67 and MMP-9 proteins in U-373MG cells were detected by CCK-8,Transwell assay,flow cytometry and WB assay,respectively.A U-373MG cell nude mouse model was established to observe the effect of caffeine on the growth of transplanted tumor.The expressions of related proteins in transplanted tumor tissues were detected by WB method.Results:Caffeine and PF573228 could significantly inhibit the proliferation,migration and invasion abilities of U-373MG cells,promote apoptosis of U-373MG cells,and inhibit the expressions of p-FAK,p-Akt,p-Rock,Ki67 and MMP-9 proteins(all P<0.05).SC79 could partially reverse the effect of caffeine on U-373MG cells.Caffeine could significantly inhibit the growth of transplanted tumors and the expressions of above related proteins in transplanted tumor tissues(all P<0.05).Conclusion:Caffeine can inhibit the proliferation,migration and invasion abilities of U-373MG cells and promote their apoptosis by inhibiting the FXU Jiazhi1, ZHANG Yun1, CHEN Dagang1, GAO Fengquan1, REN Deshuai1, WU Weidong1, DU Yan1, WANG Na2(1. Department of Neurosurgery, the Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000 Heilongjiang, China;2. Clinical Psychology Teaching and Research Office, Qiqihar Medical College, Qiqihar 161000, Heilongjiang, China) AK/AKT/ROCK signaling pathway.

关 键 词：咖啡因 人脑胶质瘤 U-373MG细胞 增殖 迁移 侵袭 凋亡 FAK/AKT/ROCK通路 

分 类 号：R739.41[医药卫生—肿瘤]