Effect of TLR1 ,TLR2,TLR6 in PBMC from patients with ovarian cancer on tumor microenvironment / 国际检验医学杂志

ABSTRACT

Objective To explore the pathogenesis of ovarian cancer by investigating the function of Toll-like receptor 1 (TLR1),TLR2 and TLR6 in peripheral blood mononuclear cell(PBMC) from patients with ovarian cancer.Methods PBMC,SK OV 3 co culture system and anti-TLR1,anti-TLR2,anti-TLR6 mAb blocking experiment were used to explore the relationship between TLR1,TLR2 or TLR6 signaling and inflammation in ovarian cancer.Quantitative real time PCR was used to measure interleukin(IL)-1β,IL-6,IL-8,and tumor necrosises factor(TNF)-α in the PBMC.MyD88,TRAF6,TANK,NF-κB and P-NFκB were observed by Western blotting.Results In the PBMC and SK-OV-3 coculture system,we found the activation of TLR signaling pathways,including significantly increased MyD88,TRAF6,TANK and P-NF-κB levels following cocultured with SK-OV-3 in PBMC from ovarian cancer patients.PBMC derived from ovarian cancer patients led to a increase in IL-1β,IL-6 and IL-8 mRNA levels after 24 hours of co-incubation with SK-OV-3 (Fold=1.74,Fold=1.92,Fold=1.65,P＜0.05),though there was no difference of TNF-a mRNA expression.In contrast to the ovarian cancer patients,coculture of PBMC derived from benign diseases controls and healthy normal controls decreased IL-1β at the mRNA level (Fold=0.71,P＜0.05;Fold=0.72,P＜0.05),furthermore the expression of MyD88,TRAF6,TANK,P-NF-κB,and NF-κB showed no changes.PBMC which treated with anti-TLR1,anti-TLR2 or-TLR6 mAb could inhibite inflammatory IL-1β (Fold=0.16,Fold=0.31,Fold=0.29,P＜0.05) and IL-6 (Fold=0.14,Fold=0.20,Fold=0.28,P＜0.05).Conclusion TLR1/TLR2/TLR6 in PBMC of ovarian cancer patients participate in the recognition of the factors.