二甲双胍联合奥沙利铂抗肿瘤作用

Effect of Metformin Combined with Oxaliplatin on Colon Cancer Transplanted Mice

目的:探究二甲双胍联合奥沙利铂对结肠癌移植瘤小鼠的抗肿瘤作用。方法:32只BALB/C雄性小鼠左前肢腋下接种c26小鼠结肠腺癌细胞,随机分为恶病质组、二甲双胍组、奥沙利铂组以及联合组,另外8只小鼠作为正常组。奥沙利铂组小鼠每周1次腹腔注射奥沙利铂注射液0.01 mg/g,同时每日灭菌蒸馏水0.1 m L/g灌胃;二甲双胍组小鼠每日给予二甲双胍0.2 mg/g灌胃,同时每周1次腹腔注射生理盐水0.02 m L/g;联合组小鼠每日给予二甲双胍0.2 mg/g灌胃,同时每周1次腹腔注射奥沙利铂注射液0.01 mg/g;正常组和恶病质组小鼠每日灭菌蒸馏水0.1 m L/g灌胃,同时每周1次腹腔注射生理盐水0.02 m L/g。每日检测小鼠体重、肿瘤大小、自发性活动、精神毛发等。连续给药42 d后,颈椎脱臼法处死小鼠,解剖分离并称重右下肢腓肠肌组织,ELISA法检测腓肠肌组织炎症因子水平,HE染色观察腓肠肌形态。结果:荷瘤小鼠体重、腓肠肌质量、腓肠肌横切面积较正常组均明显降低(均P<0.05),奥沙利铂组和联合组小鼠肿瘤重量及体积均明显减少,且联合组减少最为明显(均P<0.05),各荷瘤小鼠腓肠肌组织中IL-6及TNF-α水平较正常组均明显升高,其中二甲双胍组及联合组较恶病质组则明显下降(均P<0.05)。结论:二甲双胍联合奥沙利铂能够抑制肿瘤生长,且能延缓癌性恶液质的发生。

Objective： To investigate the antitumor effect of metformin combined with oxaliplatin on colon cancer transplanted mice. Methods： 32 male BALB/C mice,inoculated subcutaneously with murine colon adenocarcinoma C26 cells,were randomly divided into control group,metformin group,oxaliplatin group,and combination group,and 8 normal mice were chosen as normal group. The body weight,tumor size,spontaneous activity and hair were monitored daily. After 42 days of treatment,samples were collected and tested by different methods. The levels of inflammatory factors in gastrocnemius muscle were detected by ELISA,and the morphology of gastrocnemius muscle was observed by HE staining. Results： The mice body weight,gastrocnemius muscle weight and cross-sectional area in colon cancer transplanted mice were significantly lower than those in normal group（ P〈0. 05）. Compared with control group,the tumor weight and volume were significantly decreased in oxaliplatin group and combination group（ P〈0. 05）,while the tumor weight and volume in combination group were lower than those in oxaliplatin group. The levels of IL-6 and TNF-alpha in the gastrocnemius tissues decreased significantly in the order of oxaliplatin group,control group,combination group,metformin group and normal group（ P〈0. 05）.Conclusion： Metformin combined with oxaliplatin can inhibit the growth of tumor and delay the occurrence of cancer cachexia.