实用肿瘤杂志2017，Vol.32Issue(1)：33-38,6.
MK-2206联合顺铂对乳腺癌4 T1／DDP移植瘤耐药性的影响
Effect of MK-2206 plus cisplatin on the drug resistant 4T1/DDP breast tumor in mice
摘要
Abstract
Objective To investigate the effect of protein kinase B (Akt)inhibitor MK-2206 combined with cispla-tin on the drug resistance of 4T1/cisplatin (DDP)transplantation breast tumor.Methods Drug resistant 4T1/DDP trans-plantation tumor model was established with low-dose DDP induction and in vivo/in vitro tumorigenic approach in mice.The mice were then treated with intraperitoneal injection of DDP alone (0.3 g/L,once per day),or in combination with MK-2206 gavage (1 2 g/L,once per week).The mice were sacrificed 28 days afterwards.Small animal live imaging technology was applied to detect tumor growth.Western blots were used to examine the protein levels of phosphorylated-Akt and total-Akt.Immunohistochemistry was used to examine the expression of P-glycoprotein (P-gp),breast cancer resistance protein (BCRP),and matrix metalloproteinase 7 (MMP7).Results 4T1/DDP transplantation tumor mice model developed me-dium level of drug resistance.The tumor growth rates between non-resistant and resistant mice showed no significant differ-ence (P>0.05).After similar dose of DDP (0.3 g/L)treatment,drug resistant mice showed lower sensitivity than non-resistant mice (P<0.01 ).However,in the drug resistant mice treated with MK-2206(1 2 g/L)and DDP (0.3 g/L),the tumor size were significantly reduced,compared to DDP alone group (P<0.01 ).Moreover,the expression levels of P-gp, BCRP and MMP7 were all significantly reduced (P<0.05)in MK-2206 and DDP treated mice.The phosphorylation level of Akt was also decreased (P<0.01 ).Conclusion MK-2206 in combination with cisplatin can reverse the drug resist-ance of 4T1/DDP transplantation tumor,which may be mediated through the inhibition of Akt phosphorylation.关键词
乳腺肿瘤/药物疗法/抗药性,肿瘤/1-磷脂酰肌醇3-激酶/拮抗剂和抑制剂/蛋白激酶类/顺铂/药理学/肿瘤移植/疾病模型,动物Key words
breast neoplasms/drug therapy/drug resistance,neoplasm/1-phosphatidylinositol 3-kinase/antagonists&inhibitors/protein kinases/cisplatin/pharmacology/neoplasm transplantation/disease models,animal分类
医药卫生引用本文复制引用
盛佳钰,陈红风..MK-2206联合顺铂对乳腺癌4 T1／DDP移植瘤耐药性的影响[J].实用肿瘤杂志,2017,32(1):33-38,6.基金项目
国家自然科学基金（81373647）；上海市中医药事业发展三年行动计划 （）
