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Cordeiro RS. Evaluation of homeobox gene expression in cisplatin-treated mucoepidermoid carcinoma cells [dissertation]. São Paulo: Universidade de São Paulo, Faculdade de Odontologia; 2018. Corrected version. Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of salivary gland and presents higher frequency of lymph node metastasis. Genetic alterations are closely associated with carcinogenesis and also with processes of tumor metastasis. For MEC the treatment of choice most applied today is surgery followed by radiotherapy, since chemotherapy has not shown much efficiency for the treatment of these neoplasms. Among the most commonly prescribed chemotherapic drugs for cancer treatment is platinum-based cisplatin, which acts on the cell's DNA, inducing apoptosis. There is no information in the literature regarding its action mechanism on MEC including homeobox genes. These genes comprise a large and essential family of developmental regulators that are vital for cell growth and differentiation and the anomalous expression of these genes have been implicated in carcinogenesis. Therefore, this work aimed to evaluate the expression of the homeobox genes in cells derived from mucoepidermoid carcinoma treated with cisplatin. The genes evaluated in this work were: PROX1, MEIS1, HOXB5, HOXB7 and HOXB9 by RT-qPCR. Previously, cell lines derived from mucoepidermoid carcinoma UM-HMC1 UM-HMC2 and UM-HMC3A were treated with cisplatin for 24h and subsequently subjected to the RT-qPCR assays. In addition, treated and untreated samples were analyzed by the sphere-forming assay and wound assay to verify the effect of cisplatin on chemo resistant cell-related (putative tumor stem cell) properties. As results, PROX1, MEIS1 and HOXB7 were expressed among the analyzed genes. UM-HMC3A showed higher expression of these genes than the other lineages. The HOXB5 and HOXB9 genes were not expressed in the analyzed lineages. Cisplatin reduced MEIS1 expression and increased HOXB7 expression in all lineages. The PROX1 gene showed variable expression between the lineages, being expressed in UM-HMC1 only when treated with cisplatin and reduced in treated UM-HMC2 and UM-HMC3A. The number of spheres formed did not show significant difference for UM-HMC1 and UM-HMC3A, the number of spheres increased in the cisplatin-treated UM-HMC2 lineage. In the wound assay, cisplatin was able to reduce cell migration in all lineages when compared to their controls. The results suggested that PROX1 and HOXB7 may be related to more invasive mucoepidermoid carcinoma, while MEIS1 be related to its carcinogenesis and selfrenew tumoral capacity. Cisplatin is capable to affect the expression of the homeobox genes PROX1, MEIS1 and HOXB7, which were found in the mucoepidermoid carcinoma cell lines analyzed. Cisplatin does not affect sphere formation of cells, but seems to reduce the migration of mucoepidermoid carcinoma lineages.

Avaliação da expressão dos genes homeobox em células de carcinoma mucoepidermoide tratadas com cisplatina