布托啡诺调节PI3K/AKT/mTOR信号通路对膀胱癌细胞恶性生物学行为的影响  

Effect of butorphanol on malignant biological behavior of bladder cancer cells by regulating PI3K/AKT/mTOR signaling pathway

作　　者：吴秀东[1] 韦堂墙 于晓倩 WU Xiudong;WEI Tangqiang;YU Xiaoqian(Anesthesia Operation Center,Affiliated Hospital of Chengdu University,Sichuan Chengdu 610081,China;Department of Urology,Affiliated Hospital of Chengdu University,Sichuan Chengdu 610081,China)

机构地区：[1]成都大学附属医院麻醉手术中心,四川成都610081 [2]成都大学附属医院泌尿外科,四川成都610081

出　　处：《现代肿瘤医学》2024年第5期805-810,共6页Journal of Modern Oncology

基　　金：四川省科技计划项目(编号:2023JDRC0095)。

摘　　要：目的:探讨布托啡诺调节磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/AKT/mTOR)信号通路对膀胱癌细胞恶性生物学行为的影响。方法:体外培养膀胱癌细胞T24;将细胞分为对照组、布托啡诺低剂量组(1 ng/mL)、布托啡诺中剂量组(10 ng/mL)、布托啡诺高剂量组(100 ng/mL)、激活剂组(100 ng/mL布托啡诺+PI3K激动剂Recilisib 10μmol/L)、抑制剂组(100 ng/mL布托啡诺+PI3K抑制剂LY294002 50μmol/L)。CCK-8实验检测细胞增殖;流式细胞术检测细胞凋亡;Transwell检测细胞迁移和侵袭;Western blot检测细胞PI3K/AKT/mTOR信号通路相关蛋白表达;并构建异种移植肿瘤模型,称量肿瘤质量,计算肿瘤体积。结果:与对照组比较,布托啡诺低剂量、布托啡诺中剂量、布托啡诺高剂量组T24细胞OD_(450)值和迁移、侵袭细胞数目及p-PI3K、p-AKT、p-mTOR蛋白表达显著降低,细胞凋亡率显著升高,且呈剂量依赖性(P<0.05);激活剂减弱了布托啡诺抑制T24细胞增殖、迁移和侵袭,促进细胞凋亡的作用,抑制剂加强了布托啡诺抑制T24细胞增殖、迁移和侵袭,促进细胞凋亡的作用。与裸鼠对照组相比,裸鼠布托啡诺低剂量、裸鼠布托啡诺中剂量、裸鼠布托啡诺高剂量组肿瘤体积和质量显著减小,且呈现剂量依赖性(P<0.05);与裸鼠布托啡诺高剂量组比较,裸鼠激活剂组肿瘤体积、肿瘤质量显著增大(P<0.05),裸鼠抑制剂组肿瘤体积、肿瘤质量显著减小(P<0.05)。结论:布托啡诺通过抑制PI3K/AKT/mTOR信号通路抑制膀胱癌细胞增殖、迁移和侵袭。Objective:To investigate the effect of butorphanol on the malignant biological behavior of bladder cancer cells by regulating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) signaling pathway.Methods:Bladder cancer cell T24 was cultured in vitro.Cells were grouped into control group,low-dose butorphanol group(1 ng/mL),medium-dose butorphanol group(10 ng/mL),high-dose butorphanol group(100 ng/mL),activator group(100 ng/mL butorphanol+PI3K agonist Recilisib 10 μmol/L),and inhibitor group(100 ng/mL butorphanol+PI3K inhibitor LY294002 50 μmol/L).CCK-8 experiment was applied to detect cell proliferation.Flow cytometry was applied to detect cell apoptosis.Transwell was applied to detect cell migration and invasion.Western blot was applied to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins in cells and a xenograft tumor model was constructed,the tumor mass was weighed,and the tumor volume was calculated.Results:Compared with the control group,the OD_(450) value of T24 cells,the numbers of migrating and invading cells,and the expression of p-PI3K,p-AKT,and p-mTOR proteins in the low-dose,medium dose,and high-dose butorphanol groups were obviously reduced,the apoptosis rate of cells was obviously increased,in a dose-dependent manner(P<0.05).Activators weakened the inhibitory effect of butorphanol on T24 cell proliferation,migration,and invasion,promoting cell apoptosis,while inhibitors strengthened the inhibitory effect of butorphanol on T24 cell proliferation,migration,and invasion,and the promoting effect on cell apoptosis.Compared with nude mice in the control group,the tumor volume and mass in the low dose,medium dose,and high dose butorphanol groups were obviously reduced,in a dose-dependent manner( P < 0.05).Compared with nude mice in high-dose butorphanol group,the tumor volume and mass in the nude mouse activator group were obviously increased( P < 0.05),while the tumor volume and mass in the nude mouse inhibitor group were obviously reduc

关 键 词：膀胱癌 布托啡诺 PI3K/AKT/MTOR 增殖 迁移 侵袭 

分 类 号：R737.14[医药卫生—肿瘤]