阿里红多糖体内抗肿瘤作用及其机制研究

In vivo anti-tumor activities of Fomes Officinalis polysaccharide and the underlying mechanisms

目的研究阿里红多糖(Fomes Officinals polysaccharide,FOPS)抗肿瘤作用及其抑瘤机制。方法通过腋部皮下接种S180小鼠腹水制备荷瘤小鼠模型。造模后随机分为空白组、模型组、阳性对照组、FOPS低中高剂量组,每组10只。空白组与模型组灌胃生理盐水,阳性对照组腹腔注射50 mg/kg环磷酰胺,低、中、高剂量小鼠分别灌胃不同浓度(50、100、200 mg/kg)FOPS混悬液。给药15 d后,检测各组小鼠抑瘤率及脏器指数;检测外周血白细胞、淋巴细胞数目;ELISA法检测荷瘤小鼠血清TNF-α、IFN-γ、IL-2、IL-1β、IL-6等细胞因子含量;qRT-PCR法检测肿瘤组织p38MAPK、p-c-junmRNA表达;Western Blot法检测p38MAPK、p-c-jun、NF-κB、p-NF-κB蛋白表达量。结果(1)阳性对照组及FOPS低、中、高剂量组小鼠平均瘤重均显著低于模型组(P<0.05),四组小鼠抑瘤率分别为84.87%、54.29%、40.57%、30.84%。(2)与模型组比较,FOPS低剂量组小鼠脾指数、胸腺指数显著提高,白细胞数目、淋巴细胞数目显著升高(P<0.05)。(3)与模型组比较,FOPS低剂量组小鼠血清TNF-α、IFN-γ、IL-2含量显著升高(P<0.05),FOPS低、中、高剂量组小鼠血清IL-1β、IL-6含量显著降低(P<0.01)。(4)FOPS低剂量组p38MAPK、p-c-junmRNA表达水平高于模型组(P<0.05),p38MAPK、p-c-jun和p-NF-κB蛋白表达水平高于模型组(P<0.05)。结论FOPS具有显著抗肿瘤活性,其机制与上调MAPK/NF-κB信号通路中p38MAPK、p-c-jun和p-NF-κB等相关基因及蛋白的表达有关。

Objective To investigate the antitumor activity of Fomes Officinalis polysaccharide(FOPS)and the underlying mechanisms.Methods The mice tumor-bearing model was established by subcutaneous injection of S180 ascites tumor cells into the axilla.Mice were randomly divided into control group,model group,CTX group,FOPS-L group,FOPS-M group and FOPS-H group,with 10 mice in each group.The mice were treated with NS,cyclophosphamide or FOPS for 15 d.Tumor inhibition rate and organ index were assessed,and white blood cell(WBC)and lymphocyte(LYM)were measured.Serum TNF-α,IFN-γ,IL-2,IL-1βand IL-6 were detected by ELISA.The mRNA expression levels of p38MAPK and p-c-jun in tumor tissues were detected by qRT-PCR.The protein expression levels of p38MAPK,p-c-jun,NF-κB and p-NF-κB were detected by Western Blot.Results(1)The mean tumor weights in the CTX and three FOPS groups were significantly decreased compared with the model group(P<0.05).The tumor inhibition rate in the CTX and three FOPS groups(-L,-M,-H)were 84.87%,54.29%,40.57% and 30.84%,respectively.(2)Compared with the model group,the spleen index,thymus index,WBC and LYM were increased significantly in the FOPS-L groups(P<0.05).(3)Compared with the model group,the levels of TNF-α,IFN-γ,IL-2 in the FOPS-L group were significantly increased(P<0.05),while the levels of IL-1βand IL-6 in the CTX and three FOPS groups were significantly decreased(P<0.01).(4)The mRNA expression levels of p38MAPK and p-c-jun,and the protein expression levels of p38MAPK,p-c-jun and p-NF-κB in tumor tissue were significantly increased compared with the model group(P<0.05).Conclusions FOPS has significant anti-tumor activities,and the mechanism of action is related to activation of the MAPK/NF-κB signaling pathway.