胡黄连苷Ⅱ对MCF-7乳腺癌细胞自噬的影响及其作用机制研究

Effects of PicrosideII on autophagy of MCF-7 breast cancer cells and its mechanism

目的:探讨胡黄连苷Ⅱ对MCF-7乳腺癌细胞自噬及PI3K/AKT/mTOR通路的影响。方法:50只裸鼠随机分为5组,每组10只,分为模型组、3-MA组、胡黄连苷Ⅱ高剂量(100 mg/kg)、中剂量(10 mg/kg)、低剂量(1 mg/kg)组。体外培养人乳腺癌细胞MCF-7,随后移植于裸鼠体内,建立MCF-7乳腺癌皮下移植瘤模型。测量各组裸鼠体质量;测量乳腺肿瘤体积并计算出肿瘤抑制率;HE染色法观察肿瘤细胞形态;TUNEL法检测MCF-7细胞凋亡情况;Western blot检测Beclin1、PI3K、p-PI3K、AKT、p-AKT、mTOR、p-mTOR蛋白的表达。结果:胡黄连苷Ⅱ能显著抑制乳腺癌裸鼠体质量的降低(P<0.01);提高肿瘤抑制率(P<0.01);改善病理组织结果;促进MCF-7细胞凋亡;增加Beclin1蛋白的表达;降低PI3K、p-PI3K、AKT、p-AKT、mTOR、p-mTOR蛋白的表达(P<0.01)。结论:胡黄连苷Ⅱ对MCF-7乳腺癌细胞具有显著抑制作用,其机制与抑制PI3K/AKT/mTOR通路从而增强MCF-7细胞自噬有关。

AIM : To investigate the effects of PicrosideII on autophagy and PI3K/AKT/mTOR pathway in MCF-7 breast cancer cells. METHODS : Fifty nude mice were randomly divided into five groups,ten in each group,divided into model group,3-MA group,high dose (100 mg/kg),medium dose (10 mg/kg),low dose (1 mg/kg).Human breast cancer cells MCF-7 were cultured in vitro ,and then transplanted into nude mice to establish a subcutaneous transplantation model of MCF-7 breast cancer.The weight of each group of nude mice and the breast tumor volume were measured,the tumor inhibition rate was calculated.Tumor cell morphology was observed by HE staining,and the apoptosis of MCF-7 cells by TUNEL assay.Western blot was used to detect the expression of Beclin1,PI3K,p-PI3K,AKT,p-AKT,mTOR and p-mTOR proteins. RESULTS :PicrosideII significantly inhibited the weight loss of breast cancer nude mice ( P < 0.01 ),increased the tumor inhibition rate ( P < 0.01 ),improved the pathological tissue results;promoted the apoptosis of MCF-7 cells,increased the expression of Beclin1 protein,and reduced PI3K expression of p-PI3K,AKT,p-AKT,mTOR,p-mTOR protein ( P < 0.01 ). CONCLUSION : PicrosideII has a significant inhibitory effect on MCF-7 breast cancer cells,and its mechanism is related to inhibition of PI3K/AKT/mTOR pathway and enhancement of autophagy in MCF-7 cells.