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

PELEGRINA, LAURA T; SANHUEZA MARÍA ÁNGELES; ANTONELLA R. R. CÁCERES; LACONI, MYRIAM

BUENOS AIRES

Congreso; REUNION CONJUNTA DE BIOCIENCIAS; 2017

Ovarian carcinoma is one of the most common cause ofgynecologic cancer death. Previously, we demonstrated that allopregnanolone(ALLO) modifies physiological and pathological processes of the reproductivebiology. ALLO induces ovarian morphophysiological changes, being able to alterproliferation, apoptosis and angiogenesis. Many epidemiologic and in vitro studies have showncontroversial data about P4 effects in cancer. The effect of ALLO in ovariancancer is unknown. Taking into account that ALLO affects physiologicalprocesses that may be involved in carcinogenesis our hypothesis is that ALLOaffects tumor progression. In this work, 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 ALLO 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 ALLO treatment (10-11and 10-8 M; p<0.001; p<0.01 vs. controlrespectively). P4 and ALLO increased IGROV-1 migration, the maximal effectiveconcentration was 10-11 M(148 ± 14 % and 175 ± 21 % respectively; p<0.001 vs. control), measured bywound assay. None of the steroids tested modified SKOV-3 progression steps.These results showed different responses to ALLO treatment. We conclude thatALLO could affect tumor progression. The investigation of its metabolism andmolecular mechanisms could contribute to the discovery of new therapeuticalternatives.