千金藤碱通过MAPK/ERK信号通路对鼻咽癌大鼠的防治作用及对Survivin、XIAP、Bcl-2表达的影响  

Prevention and treatment of cepharanthine through MAPK/ERK signaling pathway in rats with nasopharyngeal carcinoma and its effect on Survivin,XIAP and Bcl-2

作　　者：杨静[1] 许明君[1] 王钇力[1] 衷敬华[1] YANG Jing;XU Mingjun;WANG Yili;ZHONG Jinghua(Department of Oncology, The First Affiliated Hospital of Jiangxi Medical College, Ganzhou 34100, China)

机构地区：[1]赣南医学院第一附属医院肿瘤科,江西赣州341000

出　　处：《西安交通大学学报（医学版）》2021年第4期633-638,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：江西省自然科学基金计划资助项目(No.20142BAB205038)。

摘　　要：目的探讨千金藤碱通过丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)信号通路对鼻咽癌大鼠的防治作用及对存活素(Survivin)、X连锁凋亡抑制蛋白(XIAP)、B细胞淋巴瘤/白血病-2(Bcl-2)表达的影响。方法采用皮下注射二亚硝基哌嗪(DNP)建立鼻咽癌大鼠模型,随机分为模型组、千金藤碱组、激活剂组、抑制剂组,另设对照组。检测鼻腔灌洗液中白细胞介素(IL)-1β、IL-18水平;HE染色观察鼻黏膜病理变化;TUNEL法观察鼻黏膜细胞凋亡情况;Western blotting检测鼻黏膜中ERK、p-ERK、Survivin、XIAP、Bcl-2、Bcl-2相关X蛋白(Bax)蛋白表达。结果千金藤碱组、激活剂组和抑制剂组大鼠鼻黏膜组织病理学变化较模型组明显好转,但激活剂组改善较差;与模型组比较,千金藤碱组、激活剂组和抑制剂组大鼠体质量及鼻黏膜Survivin、XIAP、Bcl-2蛋白表达升高,IL-1β、IL-18水平和细胞凋亡率及p-ERK1/2、Bax蛋白表达降低(P<0.05);与千金藤碱组比较,激活剂组大鼠体质量及鼻黏膜Survivin、XIAP、Bcl-2蛋白表达降低,鼻腔灌注液中IL-1β、IL-18水平和鼻黏膜细胞凋亡率及p-ERK1/2、Bax蛋白表达升高,抑制剂组大鼠体质量及鼻黏膜Survivin、XIAP、Bcl-2蛋白表达升高,而相应的IL-1β、IL-18水平和细胞凋亡率及p-ERK1/2、Bax蛋白表达降低(P<0.05)。结论千金藤碱对鼻咽癌大鼠具有一定防治作用,可能通过抑制MAPK/ERK通路发挥作用。Objective To investigate the preventive and therapeutic effects of cepharanthine on nasopharyngeal carcinoma rats through the mitogen-activated protein kinase(MAPK)/extracellular signal regulated kinase(ERK)signaling pathway and its effect on Survivin and X-linked inhibitor of apoptosis protein(XIAP),and B-cell lymphoma/leukemia-2(Bcl-2).Methods A rat model of nasopharyngeal carcinoma was established by subcutaneous injection of dinitrosopiperazine(DNP).Then the rats were randomly divided into model group,stephenine group,activator group,inhibitor group,and control group.Interleukin(IL)-1βand IL-18 levels in nasal lavage fluid were detected,HE staining was used to observe pathological changes of nasal mucosa,TUNEL method was used to observe cell apoptosis of nasal mucosa,Western blotting was used to detect ERK,p-ERK,Survivin,XIAP,Bcl-2,Bcl-2 associated X protein(Bax)protein expression of nasal mucosa.Results The histopathological changes of rat nasal mucosa in stephenine group,activator group and inhibitor group were significantly better than those in model group;the improvement in activator group was worse.Compared with model group,the body mass,Survivin,XIAP,and Bcl-2 protein expressions increased,while the levels of IL-1βand IL-18,the rate of apoptosis and p-ERK1/2 and Bax protein expressions decreased in cephalothin group,activator group and inhibitor group(P<0.05).Compared with cephalothin group,in activator group the body mass,Survivin,XIAP,and Bcl-2 protein expressions decreased,whereas IL-1βand IL-18 levels,the rate of apoptosis,and p-ERK1/2 and Bax protein expressions increased.In inhibitor group,the body mass,Survivin,XIAP,and Bcl-2 protein expressions increased,IL-1βand IL-18 levels,the rate of apoptosis,and p-ERK1/2 and Bax protein expressions decreased(P<0.05).Conclusion Stephaneine has a certain preventive effect on nasopharyngeal carcinoma rats,which may play an effect by inhibiting the MAPK/ERK pathway.

关 键 词：鼻咽癌 千金藤碱 丝裂原活化蛋白激酶 细胞外信号调节激酶 细胞凋亡 

分 类 号：R739.6[医药卫生—肿瘤]