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J Endocrinol Invest ; 46(12): 2609-2616, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37233978

RESUMO

PURPOSE: Clinical control of corticotroph tumors is difficult to achieve since they usually persist or relapse after surgery. Pasireotide is approved to treat patients with Cushing's disease for whom surgical therapy is not an option. However, Pasireotide seems to be effective only in a sub-set of patients, highlighting the importance to find a response marker to this approach. Recent studies demonstrated that the delta isoform of protein kinase C (PRKCD) controls viability and cell cycle progression of an in vitro model of ACTH-secreting pituitary tumor, the AtT-20/D16v-F2 cells. This study aims at exploring the possible PRKCD role in mediating Pasireotide effects. METHODS: It was assessed cell viability, POMC expression and ACTH secretion in AtT20/D16v-F2 cells over- or under-expressing PRKCD. RESULTS: We found that Pasireotide significantly reduces AtT20/D16v-F2 cell viability, POMC expression and ACTH secretion. In addition, Pasireotide reduces miR-26a expression. PRKCD silencing decreases AtT20/D16v-F2 cell sensitivity to Pasireotide treatment; on the contrary, PRKCD overexpression increases the inhibitory effects of Pasireotide on cell viability and ACTH secretion. CONCLUSION: Our results provide new insights into potential PRKCD contribution in Pasireotide mechanism of action and suggest that PRKCD might be a possible marker of therapeutic response in ACTH-secreting pituitary tumors.


Assuntos
Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/patologia , Corticotrofos/metabolismo , Corticotrofos/patologia , Proteína Quinase C-delta/metabolismo , Proteína Quinase C-delta/farmacologia , Proteína Quinase C-delta/uso terapêutico , Pró-Opiomelanocortina/genética , Pró-Opiomelanocortina/metabolismo , Pró-Opiomelanocortina/farmacologia , Hormônio Adrenocorticotrópico/metabolismo , Recidiva Local de Neoplasia/patologia , Linhagem Celular , Hipersecreção Hipofisária de ACTH/metabolismo , Linhagem Celular Tumoral
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