美洲大蠊提取物CⅡ-3对MFC荷瘤小鼠抑瘤机制的~1H-NMR代谢组学研究

Study on Antitumor Mechanism of Periplaneta americana Extract CⅡ-3 on MFC Tumor-bearing Mice Based on 1 H-NMR Metabonomics

目的:初步研究美洲大蠊提取物CⅡ-3对上皮肿瘤细胞MFC荷瘤小鼠的抑瘤机制。方法:将Balb/c小鼠随机分为模型组(生理盐水20 mL/kg)和CⅡ-3组(200 mg/kg),每组6只。在小鼠右侧腋下注射MFC细胞悬液0.2 mL后,于次日灌胃相应药物,每日1次,连续10 d。末次给药24 h后,在测量瘤体大小的基础上,采用氢-1核磁共振技术(~1H-NMR)并结合非监督型主成分分析(PCA)、监督型偏最小二乘法-判别分析(PLS-DA)和正交偏最小二乘法-判别分析(OPLS-DA),比较两组荷瘤小鼠肝组织的代谢谱并分析差异性代谢物,探索CⅡ-3抑瘤作用的潜在机制。结果:与模型组比较,CⅡ-3组荷瘤小鼠的瘤体明显减小;两组小鼠的~1H-NMR图谱存有差异;结合非监督型PCA、监督型PLS-DA、OPLS-DA结果,共确定了肝组织潜在差异性代谢物6个,分别为糖原(升高)、丙酮酸(降低)、精氨酸(降低)、羟脯氨酸(升高)、肌苷(升高)、烟酰胺(升高),主要归属于精氨酸代谢、能量代谢和核酸代谢。结论:CⅡ-3对MFC荷瘤小鼠的抑瘤作用可能与调节精氨酸代谢、能量代谢和核酸代谢有关。

OBJECTIVE:To preliminarily study the antitumor mechanism of Periplaneta americana extract C Ⅱ-3 on MFC tumor-bearing mice. METHODS:Balb/c mice were randomly divided into model group(normal saline 20 mL/kg)and CⅡ-3 group(200 mg/kg),with 6 mice in each group. MFC cell suspension(0.2 mL)was injected under the right armpit of mice. On the next day,mice were given relevant medicine intragastrically,once a day,for consecutive 10 d. 24 h after the last administration,Based on the measurement of tumor size,~1H-NMR technology combined with unsupervised PCA,supervised PLS-DA and OPLS-DA were used to compare metabolic spectrum of liver tissue from tumor-bearing mice of 2 groups,to analyze differential metabolites and to explore the potential antitumor mechanism of C Ⅱ-3. RESULTS:Compared with model group,the tumor body was significantly reduced in tumor-bearing mice of C Ⅱ-3 group.There were differences in ~1H-NMR spectra between the 2 groups. According to unsupervised PCA,supervised PLS-DA and OPLS-DA,totally six potential differential metabolites,as glycogen(increased),pyruvate(decreased),arginine(decreased), hydroxyproline(increased), inosine(increased)and niacinamide(increased), were identified in the liver tissue,which were mainly attributed to the metabolism of arginine,energy and nucleic acid. CONCLUSIONS:The antitumor effect of CⅡ-3 may be related to the regulation of arginine metabolism,energy metabolism and nucleic acid metabolism.