Ranitidine hinders radiation induced mesenchymal traits in pancreatic adenocarcinoma

NORA MOHAMAD, TAMARA GALARZA, GRACIELA CRICCO, GABRIELA MARTIN.

Congreso; LXIV Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2019

We have previously set that the antihistamine ranitidine (R) hindered growth of human pancreatic PANC-1 and BxPC3 grafts and the development of PANC-1 lung metastasis in nude mice. Two Gy irradiation increased PANC-1 tumor growth while slowered BxPC3, though increased lung metastasis in both. R reduced irradiated tumor growth rate and lung metastases.The aim of this work was to evaluate the effect of irradiation and R on epithelial to mesenchymal transition (EMT), a process associated with invasion and metastasis, in pancreatic tumors. Dedifferentiated PANC-1 and more differentiated BxPC3 tumors were irradiated (I) or not (C) with 2 Gy of gamma radiation, transplanted to non-irradiated mice, and treated with R 150 mg/kg.day, p.o.(I+R; C+R) or not (I; C). Immunohistochemistry was performed to evaluate the expression of EMT molecular markers (E-cadherin, vimentin, Slug) and of TGF-β1(a major promoter of EMT) In PANC-1 tumors epithelial marker E-cadherin was not detected in any group, while transcription factor Slug nuclear expression was similar in all of them. In C-grafts we observed a big number of vimentin (mesenchymal marker) and TGF-β1 positive cells that was even bigger in I-tumors (p