Antiangiogenesis effect of linomide in treatment of transplanted human oral carcinoma in nude mice and its relations to regulation on cytokine secretion of macrophage

Abstract

OBJECTIVE: To investigate the antiangiogenesis effect of linomide in treatment of transplanted human squamous cell carcinoma of tongue in BALB/C nude mice and to study its relations to regulation on cytokine secretion of macrophages. METHODS: An animal model was established by inoculating the human squamous cell carcinoma cell line Tca8113 into the BALB/c nu/nu nude mice. The mice were randomly divided into three groups and received linomide therapy. The microvessel density (MVD) in the tumor tissue was investigated by immunohistochemistry The productions of TNFalphaand GM-CSF of peritoneal macrophages derived from the tumor -bearing nude mice and cultured murine macrophage cell line RAW264.7 after linomide treatment were detected by ELISA assay. RESULTS: It showed that the tumor weight of mice injected intraperitoneally with 100 mg/kg d-(1), 50 mg/kg d-(1) linomide and mice of control group were 0.47+/-0.25g, 0.92+/-0.30g and 1.75+/-0.38g, respectively. The microvessel density (MVD) in tumor tissue from mice treated with linomide 100 mg/kg d-(1), 50 mg/kg d-(1) decreased 38.2%, 57.8% respectively when compared with that in mice of control group. After linomide treatment, the function of TNFalpha secretion of peritoneal macrophages from tumor-bearing nude mice was significantly inhibi ted when compared with macrophages from untreated mice. And linomide inhibited the release of TNFalpha of RAW264.7 cells in a dose dependent manner. CONCLUSION: It indicats that linomide can effectively inhibit the growth of human squamous carcinoma of tongue in nude mice and decrease the microvessel density in the tumor tissue. The affection of release of antiangiogenic factor TNFalpha of macrophage may be an important mechanism of antitumor activity of linomide.