P-glycoprotein functional activity in healthy Caucasians and patients with non-Hodgkin’s lymphoma

Cellular Therapy and Transplantation

Oleg V. Mukhin¹  Olga B. Goreva¹  Elena V. Vorontsova¹  Alevtina Y. Grishanova¹  Natalya P. Domnikova¹  Vyacheslav V. Lyakhovich¹ 

关键词: P-glycoprotein activity;    non-Hodgkin’s lymphoma;    chemotherapy resistance;   

DOI  :  10.3205/ctt-2010-No9-abstract21

学科分类：肿瘤学

来源: Universitaetsklinikum Hamburg - Eppendorf / University Medical Center Hamburg - Eppendorf

【 摘 要 】

P-glycoprotein(P-gp)functionsasatrans-membraneATP-dependentpump,decreasingtheintracellularconcentrationofdifferenttoxicsubstances,includingantineoplasticagents.P-gpactivitymayinfluencethedistributionandbioavailabilityofP-gpsubstrates,therebychangingtheresponsetochemotherapy.TheaimoftheinvestigationwastoestimatetheP-gpactivityinacontrolgroupofhealthypersonsandpatientswithnon-Hodgkin’slymphoma(NHL),andanalyzetherelationshipofP-gpfunctionwithtumormalignancygrade,chemotherapyprotocols,andtheresponsetochemotherapy.Methods:P-gpactivitywasassessedusingflowcytometricassaybasedonfluorescentP-gpsubstraterhodamine123(Rh123)effluxinhibitionbyP-gpinhibitorverapamilinlymphocytesinacontrolgroupofhealthypersons(n=49)andpatientswithNHL(n=76).Results:P-glycoproteinfunctionintreatedNHLpatientswassignificantly(р=0.02)higherthaninuntreatedpatients.ThestudyofP-gpfunctioninNHLpatientsshowedthatP-gpactivitywasassociatedwithadifferenttumormalignancygrade(p=0.01):P-gpactivityinthepatientswithhigh-gradeNHLwassignificantly(р=0.009)higherincomparisontopatientswithlow-gradeNHL.AlthoughP-gpfunctionintreatedNHLpatientstendedtobehigherinpatientswhoreceivedmoreaggressivechemotherapy,thisdifferencewasn’tstatisticallysignificant.P-glycoproteinfunctionwashigherinchemoresistantpatients(diseaseprogression)thaninthosewhoweresensitivetochemotherapy(completeorpartialremission,stabledisease),butthedifferencedidnotreachastatisticalsignificance.Inconclusion,P-gpactivitywashigherinpatientswithNHLthaninthecontrolgroupofhealthypersons,andassociatedwithtumormalignancygrade.

【 授权许可】

Unknown