Antiangiogenic therapy of human esophageal cancers with thalidomide in nude mice

Background. Thalidomide (alpha-N-phthalimidoglutarimide) is attracting new attention because of its antiangiogenic effect in corneal neovascularizatio n models. However, the effect of this agent on esophageal carcinoma is yet to be established. Methods. The human esophageal squamous cell carcinoma strains ES63 and ES80 implanted subcutaneously in nude mice were used to evaluate the antiangiog enic effect of thalidomide (200 mg/kg/d) after daily gavage or intraperiton eal administration. Tumor size was measured, and assessment of microvessel density was performed histochemically with Griffonia simplicifolia lectin I . Characterizations of angiogenic growth factors, vascular endothelial grow th factor, basic fibroblast growth factor, and thymidine phosphorylase in E S63 and ES80 tumors were done by immunohistochemical staining and reverse t ranscription-polymerase chain reaction. Results. ES63 strongly expressed 3 angiogenic factors, but ES80 showed mode rate expression of thymidine phosphorylase and only weak or no expression o f vascular endothelial grown factor and basic fibroblast growth factor at p rotein and messenger RNA levels. In ES63 intraperitoneal injection of thali domide produced significant (P < .05) inhibition of tumor growth, but there was no effect after gastric gavage. Also, a significantly (P < .0005) lowe r microvessel density was encountered in the intraperitoneal thalidomide gr oup. However, in the ES80 tumor strain thalidomide had no antiangiogenic ef fect after either intraperitoneal or oral administration. Conclusions. These data indicate that thalidomide exerts an antiangiogenic effect on solid tumor after intraperitoneal administration. Thalidomide mig ht be one of the hopeful antiangiogenic drugs for solid tumors.