宁夏密点麻蜥不同部位干预顺铂耐药胃癌模型裸鼠的效应及机制研究  

Effect and mechanism study of different parts of Ningxia Dense Point Hemp Lizard on cisplatin resistant gastric cancer model nude mice

作　　者：程翻娥 白星 李铮 李卫强[2] CHENG Fane;BAI Xing;LI Zheng;LI Weiqiang(Department of Traditional Chinese Medicine,Ningxia Medical University,Yinchuan,750004,China;Key Laboratory of Modernization of Ministry of Education of Hui Nationality Medicine)

机构地区：[1]宁夏医科大学中医学院,银川750004 [2]宁夏少数民族医药现代化教育部重点实验室

出　　处：《中国中西医结合消化杂志》2023年第3期197-203,共7页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：宁夏自然科学基金重点项目(No:2021AAC02014);国家自然科学基金项目(No:82260916)。

摘　　要：目的:通过建立人胃癌耐药细胞株MKN-45/顺铂皮下瘤裸鼠模型,探讨宁夏密点麻蜥身体不同部位联合顺铂对顺铂耐药胃癌模型裸鼠的干预作用。方法:将36只BALB/c裸鼠均注射MKN-45/顺铂单细胞悬液于右前腋侧皮下制备胃癌裸鼠顺铂耐药模型。造模成功后随机分为模型组、顺铂组、宁夏密点麻蜥头部+顺铂组、宁夏密点麻蜥四肢+顺铂组、宁夏密点麻蜥躯干+顺铂组、宁夏密点麻蜥尾部+顺铂组共6组。除模型组外,余组均给予相应药物治疗28d。测定各组裸鼠肿瘤体积大小、肿瘤重量及抑瘤率;分别采用免疫印迹法及免疫组织化学法检测各组裸鼠瘤组织中耐药相关蛋白P-糖蛋白(P-gp)、多药耐药蛋白1(MRP1)、B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达水平;采用TUNEL法检测各组裸鼠瘤组织中耐药细胞凋亡情况。结果:与模型组比较,各给药组肿瘤重量均减轻(P<0.05),各给药组中P-gp、MRP1、Bcl-2的表达均显著降低(P<0.05),Bax的表达均显著增高(P<0.05),耐药细胞凋亡率均显著增高(P<0.05);与顺铂组比较,宁夏密点麻蜥不同部位+顺铂各组肿瘤重量均明显减轻(P<0.05),以宁夏密点麻蜥尾部+顺铂组肿瘤重量减轻最显著(P<0.05),且抑瘤率最高;P-gp、MRP-1、Bcl-2的表达均降低(P<0.05),Bax的表达均升高(P<0.05),且前两者均以宁夏密点麻蜥尾部+顺铂组最明显(P<0.05);各组裸鼠瘤组织中耐药细胞凋亡率均显著增高(P<0.05),以宁夏密点麻蜥尾部+顺铂组凋亡率增高最显著(P<0.05)。结论:宁夏密点麻蜥身体不同部位联合顺铂均可有不同程度逆转胃癌裸鼠顺铂耐药的作用,以宁夏密点麻蜥尾部+顺铂组增敏提效作用最为明显。Objective:To establish a human gastric cancer resistant cell line MKN-45/DDP subcutaneous tumor model in nude mice,and to investigate the intervention of different body parts of Ningxia Dense Point Lizard combined with cisplatin on the cisplatin resistant gastric cancer model in nude mice.Methods:Thirty-six BALB/c nude mice were injected with MKN-45/DDP single cell suspension subcutively in the right anterior axillary side to prepare cisplatin resistant models of nude mice with gastric cancer.After successful modeling,they were randomly divided into 6groups:model group,cisplatin group,head+cisplatin group,all fours+cisplatin group,body+cisplatin group,and afterbody+cisplatin group.Except model group,other groups were treated with corresponding drugs for 28days.Tumor size,tumor weight and tumor inhibition rate were determined in each group.The expression levels of drug-resistant protein P-glycoprotein(P-gp),multidrug-resistant protein 1(MRP1),Bcell lymphoma-2(Bcl-2)and Bcl-2associated X protein(Bax)in tumor tissue of nude mice in each group were detected by Western blot and immunohistochemistry.TUNEL method was used to detect the apoptosis of drug-resistant cells in tumor tissue of nude mice.Results:Compared with model group,tumor weight was decreased in all treatment groups(P<0.05),the expression of P-gp,MRP1and Bcl-2in all treatment groups were significantly decreased(P<0.05),the expression of Bax was significantly increased(P<0.05),and the apoptosis rate of drug-resistant cells was significantly increased(P<0.05).Compared with cisplatin group,the tumor weight of different body parts of Ningxia Dense Point Lizard+cisplatin group was significantly reduced(P<0.05),and the tumor weight in the afterbody+cisplatin group was the most obvious reduction(P<0.05),and the tumor inhibitory rate was the highest.The expressions of P-gp,MRP1and Bcl-2were decreased(P<0.05),while the expressions of Bax were increased(P<0.05),and the first two were most obvious in the afterbody+cisplatin group(P<0.05).The apoptotic rate of drug-r

关 键 词：宁夏密点麻蜥 胃癌 顺铂 耐药性 

分 类 号：R735.2[医药卫生—肿瘤]