EVALUATION OF CALCITRIOL IN COMBINATION WITH HISTAMINE AS A THERAPEUTIC STRATEGY FOR LEYDIG CELL TUMORS IN A SYNGENEIC MOUSE MODEL

CAVALLOTI GOMEZ, ALINA; RAICES, TRINIDAD; PIGNATARO, OMAR PEDRO; ABIUSO, ADRIANA MARÍA BELÉN; BELGOROSKY, ALICIA; MONDILLO, CAROLINA; VARELA, MARÍA LUISA; BESIO MORENO, MARCOS; BERENSZTEIN, ESPERANZA

Congreso; LXV Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2020

SAIC

Leydig cell tumors (LCT) are testicular neoplasms associated with endocrine dysfunctions in boys and adults. Current therapies for benign LCT entail side effects, while malignant LCT respond poorly to chemo/radiotherapy. Hence, new treatment options are needed. Calcitriol (CAL, the active form of vitamin D) has been tested as a therapeutic approach to manage various cancers and is often assayed in combination with other drugs to potentiate its effect. Histamine (HA) receptor H1 gene has a vitamin D-response element, and we have recently found that CAL induces its expression and decreases cell proliferation in Leydig tumor cells. In turn, HA is currently used as part of certain anti-cancer regimens, and our previous reports indicate that it can reduce the steroidogenic potential of the Leydig tumor cell line MA-10 via H1 receptor. Objective: To evaluate the effectiveness of a combined CAL+HA treatment in a syngeneic murine model of LCT. Methods: In vitro: MA-10 cells were treated with CAL (10-8 -- 10-11M) or HA (10-5 - 10-9 M). StAR protein expression, cell proliferation and steroid levels were evaluated by Western blot, SRB assay and RIA, respectively. In vivo: Six-week-old male mice CB6F1 with MA-10 cell-derived tumors were treated i.p. with CAL (0.05 µg), HA (0.5 mg/kg), CAL+HA, or vehicle, thrice a week. Results: CAL reduced LCT volume in vivo (52% inhibition, p