| 金 时,耿健雄,曹守波,曹鸿艳,胡 靖.大豆苷元增强多西紫杉醇体外杀伤三阴性乳腺癌作用研究[J].,2019,19(5):842-845 |
| 大豆苷元增强多西紫杉醇体外杀伤三阴性乳腺癌作用研究 |
| Effects of Daidzein Reverse Docetaxel Resistance by Regulating the Expression of BRCA1 |
| 投稿时间：2018-05-23 修订日期：2018-06-18 |
| DOI：10.13241/j.cnki.pmb.2019.05.010 |
| 中文关键词: 三阴性乳腺癌 大豆苷元 BRCA1 凋亡 |
| 英文关键词: Triple negative breast cancer Daidzein BRCA1 Apoptosis |
| 基金项目:黑龙江省教育厅科研基金项目（12521284） |
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| 中文摘要: |
| 摘要 目的：研究大豆苷元通过调节BRCA1表达逆转多西紫杉醇耐药的具体机制。方法：应用三阴性人乳腺癌细胞系MDA-MB-231、SUM-1315作为研究对象，通过MTT法评估分析不同治疗组的抑瘤率，应用流式细胞仪检测各治疗组细胞的凋亡情况；应用western-blot分析各治疗组BRCA1及凋亡相关蛋白的表达情况。结果：研究发现大豆苷元、多西紫杉醇及联合组对乳腺癌MDA-MB-231、SUM1315细胞的抑制呈浓度依赖的原则。并且BRCA1表达的细胞系MDA-MB-231比BRCA1突变的细胞系SUM1315抑瘤率更高，两个细胞系不同治疗组分别与对照组相比较，凋亡率明显升高，均具有统计学意义；且随着大豆苷元的加入，可使多西紫杉醇的凋亡率显著增加，并且可减少多西紫杉醇的用量。在SUM-1315细胞系，大豆苷元逆转多西紫杉醇耐药，增加凋亡比率更为显著。大豆苷元可使BRCA1突变型的三阴性乳腺癌细胞系SUM-1315表达BRCA1，并具有浓度依赖性。对各组细胞的凋亡蛋白的变化进行免疫印迹分析表明大豆苷元联合多西紫杉醇可通过调节caspase依赖的凋亡通路活性来增强多西紫杉醇的凋亡作用，从而增强乳腺癌细胞杀伤。结论：大豆苷元可通过调节BRCA1表达量，协同增强多西紫杉类药物杀伤三阴性乳腺癌细胞，促进凋亡进而逆转化疗耐药。 |
| 英文摘要: |
| ABSTRACT Objective: To study the specific mechanism of daidzein to reverse docetaxel resistance by regulating the expression of BRCA1. Methods: The tri-negative human breast cancer cell line MDA-MB-231 and SUM-1315 were used as the study, and the MTT method was used to evaluate the rate of tumor grow inhibition during different treatment groups, and the cell apoptosis was detected by flow cytometry. Apoptosis related proteins expressions were analyzed by western-blot. Results: We found that the inhibition rate of the daidzein, docetaxel and combined groups were concentration-dependent in the MDA-MB-231 and SUM1315 cells. And the inhibitory rate in MDA-MB-231is higher than SUM1315. Different treatment groups compared with control group in both two cell lines, apoptosis rate increased significantly. And all groups have statistically significant. With the addition of daidzein, the apoptosis rate of docetaxel groups can be significantly increased, at the same time, the dosage of docetaxel can be reduced. In the SUM-1315 cell line, daidzein can reverse docetaxel resistance and increase apoptosis ratios. Daidzein can change the expression of BRCA1 accroding to the concentration dependence in the tri-negative breast cancer cell line. The change of apoptosis protein immunoblot analysis in each cell line showed that daidzein and docetaxel by adjusting apoptotic pathways of caspase dependent activity to enhance the apoptosis effect of docetaxel, thus improve cytotoxicity. Conclusion: This paper illustrates the daidzein enhance docetaxel killing activity and reverse the drug resistance mechanism by regulating the expression of BRCA1in tri-negative breast cancer cells. |
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