Cyclopamine Reduces the Growth of Endometrial Carcinoma and Hedgehog Pathway Proteins in a Xenograft Mouse Model

Abstract

Endometrial carcinoma is a frequently occurring malignancy of the female reproductive tract. Previous investigations have implicated the Hedgehog signaling pathway, including the smoothened (Smo) receptor, in tumor progression. Here, we established a nude mouse xenograft model of endometrial cancer to investigate the effect of the Smo receptor antagonist cyclopamine on the growth of endometrial carcinoma. Mice were randomly sorted into two groups receiving 0.2 mL/mouse every other day of either cyclopamine (20 mg/mL) or solvent (control). The growth of the mice was observed for 18 days. Then, mice were euthanized, tumors were removed and weighed, and tumor volume inhibition rate (VIR) and weight inhibition rate (WIR) were calculated. Smo, Gli1, and Gli2 mRNA expression was measured in tumor tissues by RT-PCR, and Vascular endothelial growth factor (VEGF) and CD31 were detected by immunohistochemistry. We found that cyclopamine treatment reduced the tumor growth rate and significantly reduced the volumes and weights of the transplanted tumors compared with those of the controls. Furthermore, the transplanted tumors of cyclopamine-treated mice possessed lower expression levels of Smo, Gli1, and Gli2, and displayed a lower positive expression of VEGF and CD31. Thus, the Smo receptor antagonist cyclopamine inhibited transplanted tumor growth in nude mice with endometrial carcinoma, which is likely connected with cyclopamine downregulation of Smo, Gli1, and Gli2 mRNA expression that promote angiogenesis.