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

The inhibitory effect of panax notoginseng saponins in combination with tamoxifen on human breast cancer cells and the effect on PI3K-AKT-mTOR signaling pathway

目的探讨三七总皂苷(PNS)联合三苯氧胺(TAM)对人乳腺癌细胞的抑制作用及对PI3K-AKT-m TOR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只裸鼠随机分为6组,每组11只,分别为模型对照组、单纯5 mg·kg^(-1)TAM组、100 mg·kg^(-1)PNS组、200 mg·kg^(-1)PNS组、5 mg·kg^(-1)TAM+100 mg·kg^(-1)PNS组、5 mg·kg^(-1)TAM+200 mg·kg^(-1)PNS组、连续给药30 d,每周记录裸鼠体质量,肿瘤抑制率,给药结束后分离瘤体并称重,观察瘤体病理组织学结果,采用免疫组化法检测HER-2,谷胱甘肽S转移酶(GST-л)及天冬氨酸蛋白水解酶(Caspase-3)的表达情况。结果与TAM组相比较,5 mg·kg^(-1)TAM+100 mg·kg^(-1)PNS组和5 mg·kg^(-1)TAM+200 mg·kg^(-1)PNS组肿瘤抑制率均大于单纯TAM组(P<0.05),5 mg·kg^(-1)TAM+100 mg·kg^(-1)PNS组和5 mg·kg^(-1)TAM+200 mg·kg^(-1)PNS组HER-2及GST-л表达水平显著低于单纯TAM组(P<0.05),Caspase-3表达显著高于单纯TAM组(P<0.05)。结论 PNS能显著增加TAM抗乳腺癌的作用,其机制可能与调控m TOR信号通路有关。

Objective To study the inhibitory effect of Panax Notoginseng Saponins in combination with Tamoxifen on human breast cancer cells and the effect on PI3 K-AKT-m TOR signaling pathway. Methods 70 nude mice were inoculated subcutaneously in the right breast with LCC2 cells. The 66 successful modeling nude mice were randomly divided into 6 groups and there were 11 rats in each group: model control group,5 mg·kg^(-1) TAM group,100 mg·kg^(-1) PNS group,200 mg·kg^(-1) PNS group,5 mg·kg^(-1) TAM + 100 mg·kg^(-1) PNS group,5 mg·kg^(-1) TAM + 200 mg·kg^(-1) PNS group,administrated for 30 days. The weight of nude mice and tumor inhibitory rate were recorded per week. After the end of administration,the tumor was isolated and weighed. The histopathological results were observed and the expression of HER-2,GST-л and Caspase-3 were determined by immunohistochemistry. Results Compared to the TAM group,the tumor inhibition rates of 5 mg·kg^(-1) TAM + 100 mg·kg^(-1) PNS group and 5 mg·kg^(-1) TAM + 200 mg·kg^(-1) PNS group were significantly higher than that in TAM group( P < 0. 05). The expressions of HER-2 and GST-л were significantly lower than that in TAM( P < 0. 05) and the expression of Caspase-3 was significantly higher than that in TAM( P < 0. 05).Conclusions PNS can increase the effect of TAM to confront breast cancer,which mechanism may be associated with the regulation of m TOR signaling pathway.