EFFECT OF ALLOPREGNANOLONE, A PROGESTERONE METABOLITE, OVER HUMAN OVARIAN CANCER CELL LINES PROGRESSION STEPS: POTENTIAL USE AS THERAPEUTIC TOOL.

PELEGRINA, LAURA TATIANA; SANHUEZA, MARIA DE LOS ANGELES; CACERES, ANTONELLA; RODRIGUEZ, C.E; LACONI, MYRIAM R; PELEGRINA, LAURA TATIANA; SANHUEZA, MARIA DE LOS ANGELES; CACERES, ANTONELLA; RODRIGUEZ, C.E; LACONI, MYRIAM R

Buenos Aires

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

SAIC-SAFE-SAI- SAN

EFFECT OF ALLOPREGNANOLONE, A PROGESTERONEMETABOLITE, on HUMAN OVARIAN CANCER CELL LINES PROGRESSION: POTENTIAL USE ASTHERAPEUTIC TOOL.  Pelegrina LT, Sanhueza MA, CáceresARR, Rodriguez CE, Laconi MR. Laboratoriode Fisio-patología ovárica. IMBECU-CONICET; Universidad Juan Agustín Maza. Universidad de Mendoza; Mendoza, Argentina  Ovarian carcer is one of the most commoncause of gynecologic cancer death. Allopregnanolone (ALL), a progesterone (P4)metabolite, modifies ovarian physiological and pathological processes. Changesin ALL levels during estrous cycle or under stress situations can conduce topathological alterations in ovarian development. We reported the first evidencethat ALL induces ovarian morpho-physiological changes altering proliferation,apoptosis and angiogenesis. On the other hand, epidemiologic and in vitro studies have showncontroversial data about P4 effects in cancer. The effect on P4 metabolitesover ovarian cancer is relevant and require more deep trials due to it could beinvolved on cancer progression. The hypothesis is that changes in ALL concentrationsaffects ovarian tumor progression. Here we investigated proliferation,apoptosis, clonogenic capacity and migration of human ovarian cancer cell linesIGROV-1 and SKOV-3. For this purpose, both cell lines were exposed to a rangeof P4 and ALLO concentrations (10-11-10-5 M) for 72 h. We demonstrated that ALL increasedproliferation in a concentration dependent manner by MTT, reaching a maximumeffect of 44.5 ± 13.5 % on IGROV-1 (p<0.001 vs. control: untreated cells).The IGROV-1 expression of the antigen Ki67 showed similar values toproliferation assay. Expression of cleaved caspase 3 did not change in any linestudied. IGROV-1 clonogenic capacity was increased by ALL treatment (10-11and 10-8 M; p<0.001; p<0.01 vs. controlrespectively). P4 and ALL increased IGROV-1 migration, the maximal effectiveconcentration was 10-11 M (148 ± 14 % and 175 ± 21 % respectively;p<0.001 vs. control), measured by wound assay. None of the steroids testedmodified SKOV-3 progression. These results showed different responses to ALL treatmentthat may be due to the heterogeneity present in the tumor lines. Overall,we found that ALL significantly increase malignant proliferation in humanepithelial ovarian cancer, thus inhibiting the ALL cyclic elevation could be apotential anti-cancer agent in the future.