Laboratory of Molecular Oncology, Department of Science and Technology, National University of Quilmes, Buenos Aires, Argentina.
Pathology Service, Iriarte Hospital of Quilmes, Buenos Aires, Argentina.
Anticancer Res. 2014 Sep;34(9):4761-5.
BACKGROUND/AIM: Desmopressin (dDAVP) is a synthetic peptide analog of vasopressin with antidiuretic and hemostatic properties. Recent experimental evidence have suggested that dDAVP can inhibit metastasis formation by agonist action on V2 vasopressin receptors present in both tumor and endothelial cells. We have examined the kinetics of dDAVP effect during metastatic colonization and its potential association with hemostasis.
The experimental metastasis assay was performed by injecting F3II mammary carcinoma cells into the lateral tail vein of syngeneic female BALB/c mice.
Clinically relevant doses of dDAVP (0.3 to 2 μg/kg intravenously (i.v.)) produced a dose-dependent inhibition in the formation of lung nodules when administered during the first 24 hours after F3II tumor cell injection. The hemostatic agent tranexamic acid (10 mg/kg, i.v.) had no effect on metastasis formation in the same experimental conditions, while the anticoagulant enoxaparin (1 mg/kg, subcutaneously (s.c.)) did not modify the antimetastatic action of dDAVP. In vitro, dDAVP had a strong inhibitory effect on F3II cell colony formation.
dDAVP interferes with early metastatic disease, and direct association of this effect with hemostatic mechanisms is unlikely.
背景/目的:去氨加压素(dDAVP)是一种合成的血管加压素类似物,具有抗利尿和止血作用。最近的实验证据表明,dDAVP 通过与肿瘤细胞和内皮细胞中存在的 V2 血管加压素受体的激动作用,可抑制转移形成。我们研究了 dDAVP 在转移定植过程中的作用动力学及其与止血的潜在关联。
通过将 F3II 乳腺癌细胞注射到同基因雌性 BALB/c 小鼠的尾静脉侧,进行实验性转移测定。
当在 F3II 肿瘤细胞注射后 24 小时内给予临床相关剂量的 dDAVP(0.3 至 2μg/kg 静脉内(i.v.))时,可剂量依赖性地抑制肺结节的形成。止血剂氨甲环酸(10mg/kg,i.v.)在相同实验条件下对转移形成没有影响,而抗凝剂依诺肝素(1mg/kg,皮下(s.c.))则不改变 dDAVP 的抗转移作用。在体外,dDAVP 对 F3II 细胞集落形成有强烈的抑制作用。
dDAVP 干扰早期转移疾病,并且这种作用与止血机制的直接关联不太可能。