engleski

HDACi drugs hamper experimental mouse teratoma development

Testicular Germ Cell Tumours (TGCT) are the most frequent malignancies in young males, driven by epimutations. Teratoma are TGCT composed of all three germ layer tissues. Mouse teratoma model, due to its heterogeneity and pluripotent core, is a very reliable in vitro model for investigating the effect of cancer drugs, including histone deacetylase inhibitors, on the epigenetic regulation of tumorigenicity. After isolation, mouse egg cylinders were treated for two hours with Trichostatin-A (TSA) and Valproate (VPA), respectively. Developing teratomas were cultured in vitro and measured for seven days. Proliferation (Ki-67) and apoptosis (Caspase-3) were analysed by immunohistochemistry. Gene expression of stemness/differentiation genes was analysed by qPCR. TSA and VPA induced strong growth retardation despite unchanged proliferative or apoptotic activity. Treatments exhibited opposite effects on gene expression compared to control. TSA upregulates while VPA downregulates stemness/differentiation genes. VPA downregulation of investigated genes could be responsible for reducing teratoma growth, initiating senescence. TSA upregulation of these genes points to a loss of expression regulation, with consequent growth retardation possibly being due to general teratoma dysregulation. This research confirms the effect of VPA and TSA strongly hampering cancer development. These treatments producing the same phenotypical effect of growth inhibition despite different molecular effects and no change in proliferative and mitotic activity illustrate the complex relationship between histone acetylation and regulation of biological processes.

teratoma ; HDACi

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