Endometrial cancer is one of the most frequently diagnosed
cancer in females with prevalence of 22 in 100,000 women. The etiology of the
cancer remains unclear. Despite significant progress towards understanding the patho-mechanism of the disease, effective treatment is still lacking. The results of the study suggest that combined treatment of Ishikawa cells for 24 h with
disintegrin and then for 24 h with
melphalan severely inhibits important
biological functions of the cells. We showed that such strategy have a potent cytotoxic effect. The mechanism of process undergoes probably through inhibition of
integrin - dependent signaling. In this study we shown down regulation of Shc and FAK
proteins in cells treated with
echistatin and
melphalan. It suggests that signaling pathways that involve Shc and FAK participation may represent target for
antineoplastic strategy. The functional significance of the combined treatment of Ishikwa cells with
echistatin and
melphalan was found at the level of
collagen biosynthesis. Decreased biosynthesis of
collagen in extracellular matrix may suppress cell growth and induce apoptosis. The treatment with
echistatin and
melphalan also showed decreased expression of IGF receptor in comparison to the cells treated with both compounds separately. The data presented suggest that combined
therapy with
disintegrin -
echistatin and alkyalting
drug - mephalan may represent a new approach to more effective and safe
cancer therapy.