药对“附子-白术”对裸鼠乳腺癌骨转移NF-κB通路的影响

Effect of “Aconite-Atractylodes”on Regulating NF-κB Signal Pathway in Nude Mice with Breast Cancer Bone Metastases

目的:观察附子-白术药对抑制裸鼠乳腺癌骨转移骨损伤作用,并探讨其作用机理。方法:左心室注射MDA-MB-231BO细胞法建立乳腺癌骨转移裸鼠模型;分别采用生理盐水、附子-白术药对、唑来膦酸进行干预;观察裸鼠模型的骨转移组织病理变化,TRACP染色进行破骨细胞计数,ELISA法测定骨转移组织中细胞因子TNF-α、IL6、IL-8和IL-4含量,Western-blot检测骨转移组织中NF-κB p65蛋白的表达。结果:附子-白术药对组、唑来膦酸组骨转移组织病理损伤较模型组减轻;与模型组比较,附子-白术药对组裸鼠骨转移灶中TRACP(+)细胞数量明显减少(P<0.01),骨转移组织中TNF-α、IL6和IL-8均显著降低(P<0.05,P<0.01),IL-4含量显著升高(P<0.05),NF-κB p65表达均显著降低(P<0.01)。结论:附子-白术药对抑制了乳腺癌骨转移裸鼠模型骨损伤,其机理可能与其抑制NF-κB通路活化,进而减少促炎因子TNF-α、IL6和IL-8等的分泌,并上调抑炎因子IL-4有关。

Objective ：To investigate ＂Aconite- Atractylodes＂ drugs on the inhibition of breast cancer bone metastasis in nude mice bone injury and its mechanism. Method： Nude mice models of breast cancer bone metastasis were estab- lished by left ventricular injection of MDA - MB - 231BO cells and were treated with physiological saline, ＂Aconite - At- ractylodes＂ and zoledronic acid respectively. Pathological changes in bone metastasis tissue were observed. TRACP stai- ning was used to detect osteoclast. ELISA assay was used to detect the contents of TNF - α, IL6, IL - 8 and IL - 4 cytokine and Western - blot was used to detect the expression of TNF - κB p65 protein in bone metastasis. Results ： Pathologi- cal damages of bone metastasis tissue in ＂Aconite - Atractylodes＂ group and zoledronic acid group were lower than that in the model group significantly. Compared with the model group, TRACP （ ＋ ） cell number of bone metastasis tissue in ＂Aconite- Atractylodes＂ group was significantly reduced （P 〈 0. 01 ）. TNF- α, IL- 6 and IL- 8 in bone metastasis tissue were significantly lower（ P 〈 0. 05, P 〈 0. 01 ）, IL - 4 increased significantly （ P 〈 0. 05 ） and TNF - κB p65 expression significantly lower （P 〈0.01 ）. Conclusion： ＂Aconite -Atractylodes＂ had a therapeutic effect on bone damage in breast cancer bone metastasis nude mouse model, and the mechanisms of action may be that ＂Aconite - Atractylodes＂ could inhibit the relative activity of NF - κB p65, and decrease the expression levels of TNF -α, IL - 6 and IL - 8, and increase the expression levels of IL -4.