三七总皂苷联合三苯氧胺对人乳腺癌细胞的抑制作用及对PI3K-AKT-mTOR信号通路的影响

Inhibitory effect of Panax notoginseng saponins combined with TAM oxifen on human breast cancer cells and its effect on PI3K-AKT-m TOR signal pathway

目的:探讨三七总皂苷联合三苯氧胺对人乳腺癌细胞的抑制作用及对PI3K-AKT-mRNA信号通路的影响。方法:70只裸鼠于右胸部皮下接种乳腺癌LCC2细胞,选取造模成功的66只裸鼠随机分6组,每组11只,分别为模型对照组,单纯三苯氧胺组,三七总皂苷100 mg/kg、200 mg/kg组及三苯氧胺联合三七总皂苷100 mg/kg、200 mg/kg组,单纯三苯氧胺组腹腔注射三苯氧胺5mg/kg,三七总皂苷100 mg/kg、200 mg/kg组分别灌胃给予三七总皂苷,三苯氧胺联合三七总皂苷100 mg/kg、200 mg/kg组均腹腔注射三苯氧胺5 mg/kg,并分别灌胃给予三七总皂苷100 mg/kg及200 mg/kg,模型对照组给予等体积生理盐水(NS),每日一次,连续给药30天,每周记录肿瘤抑制率,瘤体重量,给药结束后分离瘤体,观察瘤体病理学结果,免疫组化法检测HER-2,GST-л,Caspase-3的表达情况。结果:与三苯氧胺组相比较,三苯氧胺联合三七总皂苷100 mg/kg、200 mg/kg组肿瘤抑制率均明显大于单纯三苯氧胺治疗组,HER-2及GST-л表达量显著低于模型对照组,Caspase-3表达显著高于模型对照组。结论:三七总皂苷能显著协同增加三苯氧胺抗乳腺癌的作用,其机制可能与调控mTOR信号通路,逆转三苯氧胺耐药有关。

Objective： To study the suppression role of PNS combined with TAM oxifen on human breast cancer cells and its effects on the PI3 KAKT-mRNA signal pathway. Methods： Breast cancer LCC2 cells were subcutaneously inoculated in the right chest,66 successful models were randomly divided into six groups with 11 in each group： the model group,TAM group,100 mg/kg PNS group,200 mg/kg PNS group,TAM combined with 100 mg/kg PNS group and TAM combined with 200 mg/kg group. Rats in TAM group were administered 5 mg/kg TAM by intraperitoneal injection,in the middle dose and high dose of PNS groups were administered 100 mg/kg and 200 mg/kg PNS respectively,in TAM combined with 100 mg/kg PNS group and with 200 mg/kg group were administered 100 mg/kg and 200 mg/kg PNS plus 5 mg/kg TAM by intraperitoneal injection,once a day for consecutive 30 days,the tumor inhibition rate and tumor weight were recorded,tumor tissues were collected after the administration,pathological changes were observed,expressions of HER-2,GST-л and Caspase-3 were determined by immunohistochemical staining. Results： Compared with the tamoxifen group,tumor inhibition rates in tamoxifen（ 5 mg/kg） combined with100 mg/kg and 200 mg/kg Panax notoginseng saponins were higher than that in tamoxifen group（ P〈0. 05） HER-2 and GST-л were significantly lower than those in the model group（ P〈0. 05）,and the expression of Caspase-3 was significantly higher than that in the model group（ P〈0. 05）. Conclusion： PNS can increase the effect of TAM on inhibiting breast cancer,the mechanism may be associated with its regulating m TOR signal pathway.