| 盛佳钰,陈红风.MK2206对三阴性乳腺癌顺铂耐药细胞增殖及耐药性的影响[J].肿瘤学杂志,2016,22(4):251-258. |
| MK2206对三阴性乳腺癌顺铂耐药细胞增殖及耐药性的影响 |
| Study on the Proliferation and Drug Resistance of MK2206 in Cisplatin-resistant Triple Negative Breast Cancer Cells |
| 投稿时间：2015-10-08 |
| DOI：10.11735/j.issn.1671-170X.2016.04.B001 |
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| 中文关键词: 三阴性乳腺癌 多药耐药 顺铂 MK2206 |
| 英文关键词:triple negative breast cancer multiple drug resistance cisplatin MK2206 |
| 基金项目:国家自然科学基金资助项目（81373647） |
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| 摘要点击次数: 1871 |
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| 中文摘要: |
| 摘 要：［目的］探讨Akt抑制剂MK2206对三阴性乳腺癌顺铂耐药细胞株MDA-MB-231/DDP生长活性及耐药性的影响。［方法］ 使用不同浓度梯度的顺铂（DDP）、MK2206单药或联合作用于MDA-MB-231/DDP细胞，MTT法检测各药物对细胞的增殖抑制率；高效液相色谱法检测细胞内DDP药物浓度的改变；Western Blot、Real-time PCR分别检测细胞内Akt蛋白及MDR相关基因（MDR1、BCRP、MMP7、GST-π）的表达水平。［结果］ MK2206单药对MDA-MB-231/DDP细胞有明显的抑制作用，无毒剂量的MK2206可明显增强MDA-MB-231/DDP细胞对顺铂的敏感性，增加细胞内顺铂浓度，使细胞内Akt蛋白及MDR相关基因（MDR1、BCRP、MMP7、GST-π）的表达水平明显降低。［结论］ MDA-MB-231/DDP细胞的顺铂耐药性与细胞内Akt蛋白的过度表达有关，MK2206有明显的顺铂增敏作用，能部分逆转MDA-MB-231/DDP细胞对顺铂的耐药性，其机制可能与降低细胞内MDR1、BCRP、MMP7、GST-π的基因表达水平有关。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate triple negative breast cancer MDA-MB-231/DDP growth activity and drug resistance of cisplatin-resistant cell lines of Akt inhibitor MK2206. ［Methods］ Different concentrations of cisplatin (DDP)，MK2206 alone or combined were observed on the effects of MDA-MB-231/DDP cells. The drug resistance of MDA-MB-231/DDP was evaluated by MTT assay. The variation of intracellular concentration of DDP in MDA-MB-231/DDP cells was evalua-ted by the HPLC. MDR1，BCRP，MMP7，GST-π mRNA expression and phosphorate- Akt (p-Akt)/total Akt (T-Akt)protein of breast cancer cells were detected by Real-time PCR and Western Blot，respectively. ［Results］ MK2206 inhibited MDA-MB-231/DDP cell proliferation. Non-toxic doses of MK2206 could significantly enhance the sensitivity of MDA-MB-231/DDP cells to cisplatin，and increased the intracellular concentration of cisplatin. It enabled significantly reduce the expression levels of intracellular Akt protein and MDR-related genes(MDR1，BCRP，MMP7 and GST-π). ［Conclusion］ The resistance of MDA-MB-231/DDP cells is related to the overexpression of Akt protein. MK2206 can significantly increase the sensitivity to cisplatin，and it can partially reverse the MDA-MB-231/DDP cells to cisplatin resistance，which may be associated with the decreasing of the gene expression levels of MDR1，BCRP，MMP7 and GST-π. |
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