In vitro analysis of the cyclopamine effects on uterine leiomyosarcoma cells

Abstract

The leiomyoma and leiomyosarcoma are tumors of mesenchymal origin that develop in the uterus. These tumors have variable clinical behavior, compromising fertility and may even lead to death. The leiomyoma is a benign tumor commonly found in women of reproductive age. Leiomyosarcoma represents about 40% of the uterine sarcomas. Both leiomyosarcoma as leiomyomas are myometrial neoplasms that display the same pattern of cell differentiation, but with completely different clinical progression. Several studies have shown that aberrant activation of the Hedgehog signaling pathway Sonic (SHH) is related to the development of several cancer types, because they proteins play important role in cell proliferation and differentiation. In a previous study, our group evaluated the expression profile of molecules involved in the SHH pathway in mesenchymal tumors of the uterus. The SMO protein, GLI1 and SHH showed high expression in leiomyosarcomas, followed by leiomyomas and negative in adjacent normal myometrium. These results aroused the interest in evaluating the therapeutic potential of SHH inhibitors, because some of these proteins have been inhibited in other cancers with very promising results. Thus, this project aims to evaluate, in vitro, the action of cyclopamine as a Sonic Hedgehog signaling (SHH) pathway inhibitor in uterine leiomyosarcoma cells. For this, cell lines will be submitted to inactivation of SMO by treatment with cyclopamine, as previously described in the literature for other tumors. The efficiency of this inhibition will be evaluated by Western Blott to SMO and others target of the pathway (BMP4, BCL-2 and CCND1). After the confirmation of SMO inhibition, we will to evaluate the cell migration and invasion capacity. All results will be analyzed statistically.