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Antiangiogenic therapy of human esophageal cancers with thalidomide in nude mice
T Kotoh1, D K Dhar, R Masunaga
1Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Background:
Thalidomide (alpha-N-phthalimidoglutarimide) is attracting new attention because of its antiangiogenic effect in corneal neovascularization 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 antiangiogenic effect of thalidomide (200 mg/kg/d) after daily gavage or intraperitoneal 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 growth factor, basic fibroblast growth factor, and thymidine phosphorylase in ES63 and ES80 tumors were done by immunohistochemical staining and reverse transcription-polymerase chain reaction.
Results:
ES63 strongly expressed 3 angiogenic factors, but ES80 showed moderate expression of thymidine phosphorylase and only weak or no expression of vascular endothelial grown factor and basic fibroblast growth factor at protein and messenger RNA levels. In ES63 intraperitoneal injection of thalidomide produced significant (P < .05) inhibition of tumor growth, but there was no effect after gastric gavage. Also, a significantly (P < .0005) lower microvessel density was encountered in the intraperitoneal thalidomide group. However, in the ES80 tumor strain thalidomide had no antiangiogenic effect after either intraperitoneal or oral administration.
Conclusions:
These data indicate that thalidomide exerts an antiangiogenic effect on solid tumor after intraperitoneal administration. Thalidomide might be one of the hopeful antiangiogenic drugs for solid tumors.
Insights
Thalidomide demonstrated antiangiogenic effects in esophageal carcinoma models when administered intraperitoneally. This suggests thalidomide
Area of Science:
- Oncology
- Angiogenesis Research
- Pharmacology
Background:
- Thalidomide shows antiangiogenic properties in corneal neovascularization models.
- Its efficacy against esophageal carcinoma remains unestablished.
Purpose of the Study:
- To evaluate the antiangiogenic effect of thalidomide on human esophageal squamous cell carcinoma (ES63 and ES80) in vivo.
- To assess the impact of thalidomide administration route (gavage vs. intraperitoneal) on tumor growth and angiogenesis.
Main Methods:
- Utilized human esophageal squamous cell carcinoma strains (ES63, ES80) implanted in nude mice.
- Administered thalidomide (200 mg/kg/d) via daily gavage or intraperitoneal injection.
- Measured tumor size, microvessel density (histochemistry), and angiogenic factor expression (immunohistochemistry, RT-PCR).
Main Results:
- ES63 tumors showed higher expression of angiogenic factors compared to ES80.
- Intraperitoneal thalidomide significantly inhibited ES63 tumor growth and reduced microvessel density (P < .05).
- Oral thalidomide had no effect on ES63 tumors; thalidomide showed no antiangiogenic effect on ES80 tumors via either route.
Conclusions:
- Thalidomide exerts an antiangiogenic effect on solid tumors following intraperitoneal administration.
- Thalidomide shows potential as an antiangiogenic therapeutic agent for solid tumors.
