新疆阿魏乙酸乙酯部位提取物对CT-26.WT原位移植瘤模型小鼠的抑瘤作用及机制研究
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篇名: 新疆阿魏乙酸乙酯部位提取物对CT-26.WT原位移植瘤模型小鼠的抑瘤作用及机制研究
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摘要: 目的:研究新疆阿魏乙酸乙酯部位对CT-26.WT原位移植瘤模型小鼠的抑瘤作用,并探讨其作用机制。方法:将小鼠随机分为假手术组[溶剂(聚山梨酯80和食用油)]、模型组(溶剂)、顺铂对照组(5 mg/kg)和新疆阿魏乙酸乙酯部位提取物低、中、高剂量组(0.375、0.75、1.5 g/kg,以新疆阿魏乙酸乙酯部位提取物计),每组12只。除假手术组外其余各组小鼠建立CT-26.WT原位移植瘤模型,手术1周后灌胃给予相应药物,每隔2 d给药1次,连续给药10 d后,观察各组小鼠的体质量、瘤质量、肿瘤病理切片、脾指数,计算抑瘤率。采用流式细胞磁珠微阵列法(CBA)检测小鼠血清中白细胞介素12p70(IL-12p70)、干扰素γ(IFN-γ)、肿瘤坏死因子α(TNF-α)、IL-6、单核细胞趋化蛋白1(MCP-1)、IL-10的水平。结果:与假手术组比较,其余各组小鼠成功建立原位移植瘤模型,体质量均明显降低(P<0.05),模型组小鼠血清中TNF-α、MCP-1、IL-6水平明显增加(P<0.05),IFN-γ和IL-10水平明显降低(P<0.05)。与模型组比较,顺铂对照组和新疆阿魏乙酸乙酯部位提取物低、中、高剂量组小鼠瘤质量明显降低(P<0.05),其抑瘤率分别为(62.96±12.54)%、(40.74±17.34)%、(45.93±16.74)%、(57.05±14.28)%,且肿瘤细胞排列松散,有丝分裂现象及肿瘤细胞的浸润减少,顺铂对照组和新疆阿魏乙酸乙酯部位提取物中、高剂量组小鼠的脾指数明显增加(P<0.05),所有给药组小鼠血清中IL-12p70、TNF-α、MCP-1、IL-10因子水平均明显增加(P<0.05),IL-6因子水平明显降低(P<0.05),仅新疆阿魏乙酸乙酯部位提取物高剂量组小鼠血清中IFN-γ因子水平明显增加(P<0.05)。结论:新疆阿魏乙酸乙酯部位提取物对CT-26.WT原位移植瘤模型小鼠具有抑瘤作用,其机制可能与增加IL-12p70、TNF-α、IFN-γ、MCP-1、IL-10水平和降低IL-6水平有关。
ABSTRACT: OBJECTIVE: To study the anti-tumor effects of ethyl acetate extract of Ferula sinkiangensis on CT-26.WT orthotopic transplantated tumor model mice and investigate its related mechanism. METHODS: The mice were randomly divided into sham operation group [solvent (tween 80 and edible oil)], model group (solvent), cisplatin control group (5 mg/kg), low-dose, middle-dose and high-dose groups of ethyl acetate extract from F. sinkiangensis (0.375, 0.75, 1.5 g/kg calculated, by ethyl acetate extract from F. sinkiangensis), with 12 mice in each group. The mice model of CT-26.WT orthotopic transplantation tumor was established in each group except for sham operation group. They were given relevant medicine intragastrically, once every 2 days, for consecutive 10 d a week after surgery. The body weight, tumor weight, tumor pathological section and spleen index were observed in mice; inhibitory rate of tumor was calculated. The serum levels of IL-12p70, IFN-γ, TNF-α, IL-6, MCP-1 and IL-10 in rats were determined by flow cytometry microarray method (CBA). RESULTS: Compared with sham operation group, orthotopic transplantation tumer model was established successfully in other groups, and body weight of mice was decreased significantly (P<0.05). Serum levels of TNF-α, MCP-1 and IL-6 were increased significantly in model group, while IFN-γ and IL-10 levels were decreased significantly (P<0.05). Inhibitory rate of tumor were (62.96±12.54)%, (40.74±17.34)%, (45.93±16.74)%, (57.05±14.28)%, respectively. Compared with model group, tumor weight of mice were decreased significantly (P<0.05), cells were loosely arranged, as well as mitotic and infiltration of tumor cells decreased in cisplatin control group, low-dose, middle-dose and high-dose groups of ethyl acetate extract from F. sinkiangensis. Spleen indexes of mice were increased significantly in cisplatin control group, middle-dose and high-dose groups of ethyl acetate extract from F. sinkiangensis (P<0.05). Serum levels of IL-12p70, TNF-α, MCP-1 and IL-10 were increased significantly in all administration groups (P<0.05), while serum level of IL-6 was decreased significantly (P<0.05). The serum level of IFN-γ was increased significantly only in high-dose group of ethyl acetate extract from F. sinkiangensis (P<0.05). CONCLUSIONS: Ethyl acetate extract of F. sinkiangensis has the effect of inhibiting CT-26.WT orthotopic transplantation tumor model mice, the mechanism of which may be associated with up-regulation of IL-12p70, TNF-α, IFN-γ, MCP-1, IL-10 level and down-regulation of IL-6 level.
期刊: 2018年第29卷第23期
作者: 郭萍萍,李伟,张海英
AUTHORS: GUO Pingping,LI Wei,ZHANG Haiying
关键字: 新疆阿魏;乙酸乙酯部位;结肠癌;原位移植瘤;流式细胞磁珠微阵列法;小鼠;细胞因子;抑瘤率
KEYWORDS: Ferula sinkiangensis; Ethyl acetate fraction; Colon cancer; Orthotopic transplantation tumor; Flow cytometry microarray method; Mice; Cytokine; Inhibitory rate of tumor
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