生长抑素对胃癌VEGFs和VEGF受体影响的实验研究

A Randomized Trial of the VEGFs/VEGFRs Regulation by Somatostatin in Gastric Cancer

目的探讨VEGFs/VEGFRs与胃癌的恶化及不良预后的关系。方法将60例患者随机分成生长抑素预处理组和安慰剂组,采用酶联免疫法、实时定量PCR法和免疫组化法检测VEGF水平。结果生长抑素预处理组血清VEGF水平明显下降,但mRNA水平并无明显变化,并且血清VEGF水平下降是由于蛋白降解而非mRNA转录下降引起的。同时,预处理组VEGF受体-3蛋白明显下降。结论生长抑素通过下调血清VEGF水平和VEGF受体-3的表达,从而达到抗血管生成作用,为应用生长抑素治疗胃癌提供实验依据。

Objective To evaluate the correlation of expression of VEGFs and the progression and prognosis of gastric cancer.Methods We conducted an open-label,randomized trial to evaluate the activity of somatostatin in patients with primary gastric cancer treated by total gastric resection.We assessed VEGF inhibition response of this Drug by ELISA,real-time PCR and immunohistochemistry analysis.A total of 60 patients were randomly assigned to somatostatin pretreatment and placebo groups.Results Overall,pretreated with somatostatin had a significant inhibition in serum VEGF expression,but not the mRNA expression in tissue.The decrease in serum VEGF depended partially on protein synthesis and degradation but not by regulation on mRNA transcription.We also found tissue Flt-4（VEGFR-3） protein downregulation by somatostatin pretreatment.Conclusion We conclude that somatostatin exerts its anti-vasculogenic effect by downregulate serum VEGFs expression and Flt-4 expression.If more extensive studies on the somatostatin and its analogues to confirm the vasculogenesis,it may be useful as an adjuvant therapy to improve the survival of patient with gastric cancer.