阳和汤对人乳腺癌MDA-MB-231细胞增殖、凋亡及其Akt/mTOR信号通路的影响
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摘要
目的:通过阳和汤大鼠含药血清干预MDA-MB-231细胞,探索阳和汤对MDA-MB-231细胞增殖、凋亡及其Akt/mTOR信号通路的影响。方法:阳和汤含药血清(或阳性药)干预MDA-MB-231细胞24、48、72h后,CCK-8法检测细胞OD值,计算细胞抑制率。阳和汤含药血清(或阳性药)干预MDA-MB-231细胞24h后,流式细胞术检测细胞凋亡;Western blot检测细胞Akt/mTOR信号通路蛋白的表达。结果:干预24、48、72h后,与空白对照组相比,阳和汤低、高剂量组和阳性药物组细胞抑制率分别均增高(P<0.01)。干预24h后,与空白对照组相比,阳和汤低、高剂量组和阳性药物组细胞凋亡率均增高(P<0.01);Bcl-2/Bax值均降低(P<0.05或0.01)。干预24h后,与空白对照组相比,阳和汤低、高剂量组和阳性药物组mTOR磷酸化率、Akt磷酸化率均降低(P<0.05或0.01)。结论:阳和汤治疗乳腺癌的作用机制可能是通过抑制Akt/mTOR信号通路的活化,从而抑制乳腺癌细胞的增殖、诱导其凋亡,发挥抗癌作用。
Objective:MDA-MB-231 cells were intervened by Yanghe decoction medicated serum to explore the effects of Yanghe decoction on proliferation,apoptosis and Akt/mTOR signaling pathway.Methods:Medicated serum(or positive drug)was used to intervene MDA-MB-231 cells for 24 h,48 h,and 72 h,and the cell OD value was determined by CCK-8 method to calculate inhibition rate.Apoptosis was detected by flow cytometry and the levels of Akt/mTOR signaling pathway proteins were detected by western blot after intervened by medicated serum(or positive drug)for 24 h.Results:After 24,48,and 72 hof intervention,the inhibition rate of low dose group,high dose group and positive drug group increased(P<0.01).After intervention of 24 h,the apoptosis rate of low dose group,high dose group and positive drug group increased,Bcl-2/Bax value decreased,and mTOR and Akt phosphorylation rate of the low dose group,high dose group and positive drug group decreased(P<0.05 or 0.01).Conclusions:The effects of Yanghe decoction on breast cancer maybe inhibit Akt/mTOR signaling pathway to suppress proliferation of breast cancer cells and induce apoptosis.
Objective:MDA-MB-231 cells were intervened by Yanghe decoction medicated serum to explore the effects of Yanghe decoction on proliferation,apoptosis and Akt/mTOR signaling pathway.Methods:Medicated serum(or positive drug)was used to intervene MDA-MB-231 cells for 24 h,48 h,and 72 h,and the cell OD value was determined by CCK-8 method to calculate inhibition rate.Apoptosis was detected by flow cytometry and the levels of Akt/mTOR signaling pathway proteins were detected by western blot after intervened by medicated serum(or positive drug)for 24 h.Results:After 24,48,and 72 hof intervention,the inhibition rate of low dose group,high dose group and positive drug group increased(P<0.01).After intervention of 24 h,the apoptosis rate of low dose group,high dose group and positive drug group increased,Bcl-2/Bax value decreased,and mTOR and Akt phosphorylation rate of the low dose group,high dose group and positive drug group decreased(P<0.05 or 0.01).Conclusions:The effects of Yanghe decoction on breast cancer maybe inhibit Akt/mTOR signaling pathway to suppress proliferation of breast cancer cells and induce apoptosis.
引文
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[3]张君涛,王平,刘爱峰,等.中药含药血清制备方法的研究概述[J].中华中医药杂志,2015,30(11):4006-4009.
[4]窦建卫,郝云,杨亦奇,等.阳和汤治疗乳腺癌理论发微[J].世界中医药,2015,10(2):196-198.
[5]刘亚娴,田君.阳和汤含药血清对MCF-7细胞和MDA-MB-231细胞增殖抑制作用的实验研究[J].中华中医药学刊,2009,27(2):243-246.
[6]窦建卫,黄芊,赵天一,等.阳和汤对乳腺癌MDAMB-231细胞NF-κB、IL-8表达的影响[J].四川中医,2017,10(2):44-47.
[7]高永翔,沈欣,宗桂珍,等.阳和汤对裸鼠人癌移植瘤的抗肿瘤作用研究[J].中国实验方剂学杂志,2006,12(7):57-59.
[8]窦建卫,任翠翠,郝云,等.阳和汤对裸鼠荷人乳腺癌组织中CD90表达的影响及其抑瘤作用[J].世界中医药,2015,10(3):391-393.
[9]窦建卫,黄芊,赵天一,等.阳和汤对三阴性乳腺癌裸鼠移植瘤生长及IL-6、MMP-9表达的影响[J].中国现代医药杂志,2016,18(12):1-4.
[10]田莎,王云丹,黄立中,等.阳和汤对裸鼠移植性乳腺癌骨转移模型作用机制的探讨[J].湖南中医药大学学报,2012,32(7):27-30.
[11]Costa R,Han H,Gradishar W.Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer:a review[J].Breast Cancer Research&Treatment,2018,169(3):397-406.
[12]Ding X,Shen M,Xu L,et al.mTOR,breast cancer[J].Oncology Letters,2013,5(5):1554-1558.
[13]秦勇,马清涌,党晓燕,等.白藜芦醇抑制胰腺癌裸鼠移植瘤生长的实验研究[J].陕西医学杂志,2016,45(10):1275-1278.
[14]高珊.左归丸对卵巢早衰小鼠性激素及Bcl-2/Bax表达的影响[J].陕西中医,2017,38(9):1306-1307.
[15]Linjawi A,Kontogiannea M,Halwani F,et al.Prognostic significance of p53,bcl-2,and Bax expression in early breast cancer[J].Journal of the American College of Surgeons,2004,198(1):83-90.