中医药学报2016,Vol.44Issue(1):36-40,5.
蝎毒多肽对白血病干细胞 MDR1 mRNA和P-gp表达的影响
Effect of PESV on Expression Levels of MDR1mRNA and P-gp in Leukemic Stem Cells
摘要
Abstract
Objective:To investigate the impact of PESV ( peptide extract from scorpion venom ) on the expression level of MDR1 mRNA and P-gp in multi-drug-resistant leukemia stem cells .Methods:Take K562/A02 cell line for exam-ple, immunomagnetic beads were used to select cells in log phase of growth , then confirm the drug resistance with CCK-8 method.The drug-resistant K562/A02 stem cells were inoculated to right subaxillary of BABL/c nude mice to form tumor block , then tumor blocks were subcutaneously embedded into the nude mice to establish stable drug -resist-ant leukemia models.Model mice were randomly divided into six groups:a model control group ,an ADM group,a PESV group(middle dose),an ADM+PESV high dose group (high dose group),an ADM+PESV middle dose group (middle dose group ) and an ADM+PESV low dose group ( low dose group ) .The model control group received an equal volume of 0 .9%sodium chloride solution by means of intraperitoneal injection , and other groups received the corresponding dose of ADM and ( or) PESV in the same way.All groups were continuously medicated for 14 days.On the 21st day,the transplanted tumor growth was observed in nude mice in each group ,and then detect P-gp expression level of the tumor tissues in each group by flow cytometry ,then test MDR-1mRNA expression level of the tumor tissues in each group by RT-PCR method.Results: Before and after K562/A02 cells were selected with immunomagnetic beads , CD34 +CD38-cell ratio and drug-resistant dose were 31.5%(60.33 ±10.68)ug/ml,92.8%(58.33 ±9.72)ug/ml respec-tively.After the selection, commitment of the cells was significantly improved , while no difference of drug -resistance was shown .Tumor formation rate of model mice in each group was 100%,and P-gp expression results were respectively as follows:89.8% in model control group, 91.9% in ADM group, 88.4% in PESV group, 53.9% in high -dose group, 78.0%in middle dose group, 78.7%in the low-dose group.Therefore, we speculated that PESV plus ADM reduced P-gp expression , and the expression level showed a concentration -dependent manner to PESV .The results of MDR1 mRNA expression level were as follows:PESV group>low dose group>high dose group>middle dose group>ADM group,which showed a higher expression level in PESV group , middle dose group and low -dose group.Above all, we supposed that the expression level of P -gp and MDR1mRNA had a certain consistency .Conclusion: PESV re-duces the drug resistance of K 562/A02 stem cell to ADM, and it shows a positive correlation to the dose of PESV .The mechanism may be that PESV regulates the expression of P -gp and MDR -1 mRNA and enhances the sensitivity of K562/A02 stem cells to ADM .关键词
蝎毒多肽/K562/A02/P-糖蛋白/MDR-1Key words
PESV/K562/A02/P-gp/MDR-1分类
医药卫生引用本文复制引用
杨向东,史哲新,姚芳,闫理想,李德冠,杨文华,颜田赅,王兴丽,杨曦..蝎毒多肽对白血病干细胞 MDR1 mRNA和P-gp表达的影响[J].中医药学报,2016,44(1):36-40,5.基金项目
天津市科委课题(12JCQNJC09000);天津市教委课题 ()