Schirner M, Schneider M R
Research Laboratories of Schering AG Berlin, FRG.
Prostaglandins. 1991 Nov;42(5):451-61. doi: 10.1016/0090-6980(91)90036-f.
Since an involvement of platelet aggregation in the metastatic process has been found, platelet activation inhibitors were investigated for their potential to reduce tumor metastases. Recent in-vitro and in-vivo investigations showed an antimetastatic effect of prostacyclin (PGI2) and stable prostacyclin analogues. This study concentrates on the effect of the stable prostacyclin analogue Cicaprost (Schering AG) on tumor metastases in two metastasizing tumors of rodents. C57BL/6 mice bearing s.c.-implanted M5076 reticulum sarcoma were treated with Cicaprost in doses of 0.1-1.0 mg/kg throughout the experiment. Cicaprost in all doses tested reduced the number of liver metastases in a statistically significant manner. The 1.0 mg/kg dose, which decreases the median number of liver metastases to more than 93% compared to the control, was most effective. Cicaprost in the 0.5 mg/kg dose reduced the number of liver metastases in mice bearing i.v.-implanted M5076 reticulum sarcoma. In Cop-Fisher rats bearing s.c.-implanted spontaneously metastasizing R3327 MAT Lu prostate carcinoma, Cicaprost in a dose of 1.0 mg/kg p.o. daily strongly reduced the number of lung metastases. These results indicate that Cicaprost is a potent inhibitor of tumor metastases in different tumor models in rodents.
由于已经发现血小板聚集参与转移过程,因此对血小板活化抑制剂减少肿瘤转移的潜力进行了研究。最近的体外和体内研究表明,前列环素(PGI2)和稳定的前列环素类似物具有抗转移作用。本研究集中于稳定的前列环素类似物西卡前列素(先灵公司)对啮齿动物两种转移性肿瘤中肿瘤转移的影响。在整个实验过程中,对皮下植入M5076网状细胞肉瘤的C57BL/6小鼠给予0.1-1.0mg/kg剂量的西卡前列素治疗。所有测试剂量的西卡前列素均以统计学显著方式减少了肝转移灶数量。1.0mg/kg剂量最为有效,与对照组相比,该剂量可使肝转移灶中位数减少超过93%。0.5mg/kg剂量的西卡前列素减少了静脉内植入M5076网状细胞肉瘤小鼠的肝转移灶数量。在皮下植入自发转移的R3327 MAT Lu前列腺癌的考普-费舍尔大鼠中,每天口服1.0mg/kg剂量的西卡前列素可显著减少肺转移灶数量。这些结果表明,西卡前列素在啮齿动物的不同肿瘤模型中是一种有效的肿瘤转移抑制剂。