GCS在人乳腺癌细胞多药耐药中的作用及与P-gp的关系  

Glucosylceramide in multidrug resistance of MCF-7/Adr cells and its relationship with P-gp

作　　者：胡萍萍[1] 陈同钰[1] 田波[1] 蒋敬庭[2] 邓海峰[2] 李敏[2] 

机构地区：[1]苏州大学附属第三医院病理科,江苏常州213003 [2]苏州大学附属第三医院肿瘤生物诊疗中心,江苏常州213003

出　　处：《实用肿瘤杂志》2007年第6期488-491,共4页Journal of Practical Oncology

摘　　要：目的探讨葡萄糖神经酰胺合成酶(GCS)在人乳腺癌细胞多药耐药中的作用及其与P-糖蛋白(P-gp)的关系。方法采用MTT法检测多柔比星(阿霉素)对人乳腺癌耐药细胞株MCF-7/Adr和敏感株MCF-7的抑制率和IC50。以GCS抑制剂D,L-threo-1-phenyl-2-decanoyl-amino-3-morpholino-1-propanol(PDMP)预处理MCF-7/Adr后检测抑制率和IC50。运用流式细胞术(FCM)检测人MCF-7及MCF-7/Adr中GCS、P-gp的表达,以PDMP预处理细胞后检测GCS、P-gp的表达。FCM法检测细胞中ADM的荧光强度。结果MCF-7/Adr对MCF-7的耐药倍数为22.7倍,PDMP作用后阿霉素对MCF-7/Adr的抑制率升高,IC50下降(P<0.05)。MCF-7/Adr中GCS和P-gp的表达均高于MCF-7,PDMP使MCF-7/Adr中GCS表达下降(P<0.05),对P-gp表达无明显影响(P>0.05)。FCM检测显示PDMP可使阿霉素在MCF-7内潴留增多。结论GCS在MCF-7/Adr多药耐药中起重要作用,PDMP能影响P-gp功能,GCS与P-gp有一定关系。Objective To investigate the effect of glucosylceramide（GCS） on the multidrug resistance（MDR） of MCF- 7/Adr cell line, and to explore the relationship between GCS and P-gp. Methods Cytotoxity assay was tested by MTT method to get IC50of adriamycin on MCF-7 and MCF-7/Adr cells before and after treatment with GCS inhibitor D,L-threo-1- phenyl-2-decanoyl-amino-3-morpholino-l-propanol（PI）MP）. Flow cytometry（FCM） was used to test the expression of GCS and P-gp on MCF-7 and MCF-7/Adr cells. The mean fluorescent intensity of adriamycin inside MCF-7/Adr cells was obtained by FCM. Results The drug resistance of MCF-7/Adr cells was about 23 times higher than that of MCF-7. The pretreatment with PDMP could sensitize MCF-7/Adr cells to adriamycin. The expression of GCS and P-gp on MCF-7/Adr cells was stronger than that on MCF-7. PDMP reduced GCS expression on MCF-7/ADR cells,with no the changes of P-gp expression. FCM test indicated that PDMP enhanced retention of adriamycin inside MCF-7/Adr cells. Conclusion GCS may be related to multidrug resistance of MCF-7/Adr cells.

关 键 词：P-糖蛋白 抗药性 多药 乳腺肿瘤/酶学 葡萄糖转移酶类/代谢 流式细胞术 乳腺肿瘤/病理学 

分 类 号：R737.9[医药卫生—肿瘤]