Artículo Científico
Effect of progesterone and first evidence about allopregnanolone action on the progression of epithelial human ovarian cancer cell lines
Fecha
2020-02Registro en:
0960-0760
Autor
Pelegrina, Laura Tatiana
Sanhuesa, María de los Ángeles
Cáceres, Antonella Rosario Ramona
Cuello Carrión, Dario
Rodríguez, Cristina Elisa
Laconi, Myriam Raquel
Institución
Resumen
ARTÍCULO PUBLICADO EN REVISTA EXTERNA. Ovarian carcinoma is one of the most common cause of death by gynecologic cancer. Several epidemiological and in vitro studies have shown controversial data about progesterone effects in ovarian cancer. Progesterone can be converted in its active metabolite, allopregnanolone, its effects in ovarian cancer are still unknown. Previously, we demonstrated that allopregnanolone modifies ovarian morphophysiology, being able to alter
critical process of tumor development such as proliferation, apoptosis and angiogenesis. Taking into account
these antecedents, we investigated the effect of progesterone and allopregnanolone on proliferation, apoptosis,
clonogenic capacity and migration on two epithelial human ovarian cancer cell lines, IGROV-1 and SKOV-3. To
this end, IGROV-1 and SKOV-3 cells were exposed to a range of progesterone and allopregnanolone concentrations
(10-11 to 10-5 M) for 72 h. Proliferation was analyzed by MTT and Ki67 expression. Apoptosis was
measured by immunocytochemistry of cleaved caspase 3. Clonogenic capacity was evaluated by counting colonies.
Migration was analyzed by wound assay. We found that allopregnanolone increased proliferation and
Ki67 expression respect to control on IGROV-1 cells, while expression of cleaved caspase 3 did not change in any
cell line studied. IGROV-1 clonogenic capacity was also increased by allopregnanolone treatment. Both steroids,
progesterone and allopregnanolone, increased IGROV-1 migration in a concentration dependent manner. None
of the steroids tested modified SKOV-3 biological behavior analized. This is the first evidence that allopregnanolone,
a progesterone metabolite, affects critical events in tumor development of human epithelial ovarian
cancer. These results could have an impact in the future in clinic diagnosis, prognosis and treatment of ovarian
cancer patients. The regulation of progesterone and allopregnanolone steroideogenesis and their molecular
mechanisms might be considered as potential therapeutic tool in ovarian cancer. Sitio de la revista: https://www.sciencedirect.com/science/article/pii/S0960076019301013?via%3Dihub