Sola F, Farao M, Ciomei M, Pastori A, Mongelli N, Grandi M
Experimental Oncology Department, Pharmacia Research Center, Nerviano, Italy.
Invasion Metastasis. 1995;15(5-6):222-31.
FCE 27266, 2,2,'-(carbonyl-bis(imino-N-methyl-4,2-pyrrole carbonyl-imino¿N-methyl-4,2-pyrrole¿carbonylimino])-bis- (1,5-naphthalene) disulfonic acid, is a noncytotoxic compound able to complex bFGF, PDGF beta, IL-8, VEGF and IL-1 beta and to inhibit the binding to their receptors. A single intravenous treatment 48 h prior to intravenous injection with tumor cells was associated with 60% inhibition of lung metastasis from B16F10 murine melanoma and 82% inhibition of liver metastasis from M5076 murine reticulosarcoma. Marginal inhibition was observed in the latter model, administering the drug 24 h after tumor cell injection. Efficacy was maintained in athymic mice, with 95 and 100% inhibition of lung metastasis from B16F10 melanoma and A375 human melanoma. The antimetastatic activity was confirmed in two models of spontaneous metastasis: in Lewis lung carcinoma implanted intramuscularly, daily intraperitoneal treatment from day 1 to 17 was associated with 77% inhibition of lung metastasis; on M5076 reticulosarcoma implanted intramuscularly, daily intraperitoneal treatment from day 1 to 14 prior to amputation of the tumor was associated with significant inhibition of liver metastasis (79%); conversely, daily intraperitoneal treatment from day 15 to 28 starting 1 day after amputation was marginally effective. The administered doses did not inhibit the growth of the primary tumor in both models. It is concluded that FCE 27266 is a novel, promising molecule, with significant efficacy on lung and liver metastases of murine and human origin; its mode of action is still under study and is probably exerted through inhibition of growth factors and cytokines influencing the different steps of angiogenesis and metastasis.
FCE 27266，即2,2'-（羰基双（亚氨基 - N - 甲基 - 4,2 - 吡咯羰基 - 亚氨基 - N - 甲基 - 4,2 - 吡咯 - 羰基亚氨基）） - 双 - （1,5 - 萘）二磺酸，是一种无细胞毒性的化合物，能够与碱性成纤维细胞生长因子（bFGF）、血小板衍生生长因子β（PDGF beta）、白细胞介素 - 8（IL - 8）、血管内皮生长因子（VEGF）和白细胞介素 - 1β（IL - 1 beta）结合，并抑制它们与受体的结合。在静脉注射肿瘤细胞前48小时进行单次静脉治疗，可使B16F10小鼠黑色素瘤的肺转移抑制率达60%，M5076小鼠网状细胞肉瘤的肝转移抑制率达82%。在后者模型中，于肿瘤细胞注射后24小时给药，观察到的抑制作用微弱。在无胸腺小鼠中，该药物对B16F10黑色素瘤和A375人黑色素瘤肺转移的抑制率分别为95%和100%，其疗效得以维持。在两种自发转移模型中均证实了其抗转移活性：在肌肉注射植入的Lewis肺癌模型中，从第1天至第17天每天进行腹腔内治疗，可使肺转移抑制率达77%；在肌肉注射植入的M5076网状细胞肉瘤模型中，在肿瘤切除前从第1天至第14天每天进行腹腔内治疗，可显著抑制肝转移（79%）；相反，在肿瘤切除后第1天开始从第15天至第28天每天进行腹腔内治疗，效果微弱。在两种模型中，所给药剂量均未抑制原发肿瘤的生长。结论是，FCE 27266是一种新型且有前景的分子，对源自小鼠和人类的肺和肝转移具有显著疗效；其作用方式仍在研究中，可能是通过抑制影响血管生成和转移不同步骤的生长因子和细胞因子来发挥作用。
