Uso combinado de inhibidores de NFkB1 7082 y antineoplásicos convencionales como estrategia terapéutica en células tumorales linfoides humanas.

CAVALIERE VICTORIA; PAPADEMETRIO DANIELA; BLANCO GUILLERMO; GARCIA MARIANA; ALANIZ LAURA; CORDO RUSSSO ROSALÍA; HAJOS SILVIA; ALVAREZ ELIDA

Bioquímica y Patología Clínica

Asociacion Bioquimica Argentina

Lugar: Buenos Aires; Año: 2006 vol. 70 p. 43 - 60

NFkB constitutive activation participates in the development of leukemia and lymphomas generating antiapoptotic signals that promote differentiation and survival. The effectiveness of chemotherapeutic agents relies on their ability to induce apoptosis. The aim of the present study was to characterise by inmunophenotyping a cell line established in our laboratory, evaluate the effect of Doxorubicine (DOX), Vincristine (VCR) and NFkB inhibitors (CAPE - MG-1329) either alone or in combination on the cell line, and analyse the expression of apoptosis regulatory proteins. After 24 hs, all treatments were able to inhibit cell growth which resulted in a significant apoptosis induction after 48 hs. The combination of chemotherapeutic agents and NFkB inhibitors was significantly effective at 48 hs. The drugs down-regulated the expression of antiapoptotic proteins but only CAPE and MG-132 up-regulated the proapoptotic member, Bax. We conclude that the established cell line corresponds to mature B lymphocytes, sensitive to the tested drugs, whose survival mechanism depends on NFkB, raising the possibility of combining traditional chemotherapeutic agents with NFkB inhibitors to improve the patient outcome.      Key words: apoptosis, leukemias, NFkB, Doxorubicine, Vincristine, caffeic acid phenylethyl ester, MG-132.