蟾毒灵与紫杉醇协同抑制乳腺癌细胞增殖的机制  

The mechanism of Bufalin and paclitaxel synergistically suppress the proliferation of breast cancer cells

作　　者：闫顺朝[1] 焦昕[2] 李凯[1] 邹华伟[1] 

机构地区：[1]中国医科大学附属盛京医院肿瘤科,辽宁沈阳110022 [2]沈阳市胸科医院呼吸一科,辽宁沈阳110044

出　　处：《现代肿瘤医学》2016年第20期3173-3176,共4页Journal of Modern Oncology

基　　金：国家自然科学基金项目资助(编号:81302313)

摘　　要：目的:研究蟾毒灵(Bufalin)与紫杉醇是否可协同抑制乳腺癌细胞增殖,探索可能的协同机制。方法:采用MTT法测定细胞活力、采用流式细胞术检测细胞凋亡,采用Western Blot法检测AKT、p-AKT、p38、pp38、β-actin蛋白的表达。结果:MTT结果显示紫杉醇和Bufalin可以剂量依赖方式抑制乳腺癌MCF-7细胞增殖。两药联合作用可协同抑制MCF-7细胞增殖。流式分析显示40nmol/L的紫杉醇作用24小时可诱导乳腺癌MCF-7发生明显的G2M期阻滞和12.5%的细胞凋亡,10nmol/L的Bufalin作用24小时未诱导明显的细胞凋亡,10nmol/L的Bufalin与40nmol/L的紫杉醇联合作用24小时后可诱导23.7%的MCF-7细胞凋亡。Western Blot分析显示紫杉醇作用后导致AKT和p38的活化,Bufalin与紫杉醇联合作用后可抑制紫杉醇诱导的AKT活化,增强紫杉醇诱导的p38活化。结论:Bufalin可通过抑制AKT的活化、上调p38的活化与紫杉醇协同抑制乳腺癌细胞增殖,诱导细胞凋亡。ObjectiveTo investigate whether Bufalin and paclitaxel could synergistically suppress the proliferation of breast cancer cells and explore the possible mechanism. Methods ： Cells proliferation was measured using MTT as-say. Cells apoptosis was determined by flow cytometry. Expression of AKT,p - AKT,p38,p - p38 and p - actin was analyzed by Western blotting. Results ： Paclitaxel and Bufalin could synergistically suppress the proliferation of breast cancer cells. Flow cytometry analysis showed that40nmol/L of paclitaxel induced significantly G2M arrest and 12. 5% apoptosis in MCF -7 cells after 24h treatment. Bufalin （lOnmol/L） did not induce significantly apoptosis after 24h treatment. In contrast, treatment with Bufalin ＋ paclitaxel increased the apoptotic fraction from 12. 5% to 23. 7% . Fur-ther analysis showed that paclitaxel treatment activated AKT and p3 8. Bufalin could significantly down -regulate the paclitaxel - induce AKT activation and up - regulate the activation of p38. Conclusion ： Bufalin and paclitaxel could synergistically suppress the proliferation and induce apoptosis of breast cancer cells through downregulating the activi-ty of AKT and upregulating the activity of p38.

关 键 词：蟾毒灵 紫杉醇 乳腺癌 协同 凋亡 

分 类 号：R737.9[医药卫生—肿瘤]