桑黄多糖调控PI3K/AKT/mTOR通路抑制肝癌腹水荷瘤小鼠及对化疗的减毒增效作用

Mulberry polysaccharides improves the chemotherapy of liver cancer ascites tumor-bearing mice by regulating the PI3K/AKT/mTOR pathway

目的:研究桑黄多糖通过调控PI3K/AKT/mTOR通路对肝癌腹水荷瘤小鼠化疗的增效减毒作用。方法:SPF级雄性昆明种小鼠90只,随机分为正常组、模型组、环磷酰胺组、桑黄多糖组及桑黄多糖+环磷酰胺组。制备肝癌腹水荷瘤小鼠,各给药组分别给予30 mg/kg的环磷酰胺或(和)200 mg/kg的桑黄多糖,灌胃给药。正常组及模型组灌胃10 mL/kg的生理盐水。观察小鼠抑瘤率、肝脏、脾脏等指数、肿瘤组织内VEGF与炎性因子含量、PI3K/AKT/mTOR通路相关蛋白表达。结果:环磷酰胺组、桑黄多糖组及桑黄多糖+环磷酰胺组小鼠体质量、瘤体质量、肿瘤组织内血管内皮生长因子(VEGF)、肿瘤坏死因子(TNF-α)、白介素(IL)-6、PI3K、AKT及mTOR磷酸化水平均低于模型组,IL-1β水平高于模型组;桑黄多糖+环磷酰胺组小鼠体质量、抑瘤率、肿瘤组织内VEGF、TNF-α、IL-6、PI3K、AKT及mTOR磷酸化水平高于桑黄多糖组及环磷酰胺组,瘤体质量及IL-1β水平低于桑黄多糖组及环磷酰胺组(P<0.05)。结论:桑黄多糖联合环磷酰胺可有效抑制肝癌腹水荷瘤小鼠肿瘤的增殖,发挥减毒增效作用,其机制可能与下调PI3K/AKT/mTOR通路的表达有关。

AIM:To study the synergistic and attenuating effects of mulberry polysaccharides on the chemotherapy of liver cancer ascites tumor-bearing mice by regulating the PI3K/AKT/mTOR pathway.METHODS:Ninety SPF male Kunming mice were randomly divided into normal group,model group,cyclophosphamide group,mulberry polysaccharide group and mulberry polysaccharide+cyclophosphamide group.Liver cancer ascites tumor-bearing mice were prepared,and each administration group was given 30 mg/kg of cyclophosphamide or(and)200 mg/kg of mulberry polysaccharide and administered orally.The normal group and the model group were administrated with 10 mL/kg saline.The tumor suppression rate,liver,spleen and other indexes,tumor tissue VEGF and inflammatory factor content,and PI3K/AKT/mTOR pathway-related protein expression were observed in mice.RESULTS:Cyclophosphamide group,mulberry polysaccharide group and mulberry polysaccharide+cyclophosphamide group mice body weight,tumor mass,tumor tissue VEGF,TNF-α,IL-6,PI3K,AKT and mTOR phosphorylation levels were lower than the model group,and the level of IL-1βwas higher than the model group;mulberry polysaccharide+cyclophosphamide group mice were observed with body weight,tumor inhibition rate,tumor tissue VEGF,TNF-α,IL-6,PI3K,AKT and The mTOR phosphorylation level higher than the mulberry polysaccharide group and cyclophosphamide group,and the tumor mass and IL-1βlevel were lower than the mulberry polysaccharide group and cyclophosphamide group(P<0.05).CONCLUSION:Morus alba polysaccharide combined with cyclophosphamide can effectively inhibit tumor proliferation of liver cancer ascites tumor-bearing mice and exert attenuating effect.The mechanism may be related to the down-regulation of PI3K/AKT/mTOR pathway expression.