Heparanase regulates VEGF-C expression in vitro and its effect on pancreatic ductal cell adenocarcinoma / 中华普通外科杂志

ABSTRACT

Objective To measure HPSE and VEGF-C expression in pancreatic cancer tissues and to observe the effect of small interfering RNA targeting heparanase gene on VEGF-C expression and malignant biological behavior of pancreatic cancer cell lines BxPC-3.Methods We measured the relative mRNA levels of HPSE and VEGF-C in 34 pancreatic ductal cell adenocarcinoma(PDAC) specimens by RT-qPCR.The recombinant plasmid GV230/HPSE was constructed.BxPC-3 was transiently transfected with GV230/HPSE and HPSE-siRNA.The expression levels of HPSE and VEGF-C were measured by performing florescent real-time quantitative PCR (RT-qPCR) and immunoblotting.The invasion and migration potential of treated BxPC-3 was evaluated by transwell invasion assay and Scratch-wound assay.Results Spearman rank correlation analysis indicated a positive correlation between HPSE and VEGF-C (r =0.812,P ＜0.01)in pancreatic cancer tissues.HPSE and VEGF-C overexpression was correlated with tumor differentiation,lymph node metastasis and TNM stage(all P ＜0.01).RT-qPCR and Western blot showed high expression of HPSE mRNA and VEGF-C mRNA in GV230/HPSE group than that in control group,compared to low expression of HPSE mRNA and VEGF-C mRNA in siRNA group (all P ＜ 0.01).Invasion chamber assay and Scratch-wound assay showed higher invasion in GV230/HPSE group than that in control group,while lower invasion in siRNA group (all P ＜ 0.01).Conclusions Joint detection of HPSE and VEGF-C may be of significance in predicting prognosis of patients with pancreatic cancer.HPSE regulates the expression of VEGF-C and facilitates invasion and migration of BxPC-3 in vitro.