THE EFFECT OF PENTOXIFYLLINE ON SPONTANEOUS AND EXPERIMENTAL METASTASIS OF THE MOUSE NEURO2A NEUROBLASTOMA

Pentoxifylline (PTX) has been reported to have both direct and indirec t anti-tumor effects in experimental tumor models. We studied the effe ct of PTX on (1) the proliferation of Neuro2a mouse neuroblastoma cell s in vitro and in vivo, (2) spontaneous and experimental metastasis, ( 3) tumor cell membrane fluidity and (4) adhesion to a fibronectin-coat ed surface, PTX significantly reduced the proliferation of Neuro2a cel ls in vitro as determined by DNA measurement (P < 0.01) and total cell count (P < 0.02). In vivo, PTX reduced the growth of subcutaneously t ransplanted primary tumors in syngeneic A/J mice (P < 0.01; n = 15), A ll seven animals (100%) receiving intravenous tumor cells developed ex tensive liver metastasis, In contrast, only 1/11 (9%) of animals pre-t reated with oral PTX and injected with PTX-treated cells developed liv er metastases. Of five mice receiving PTX-treated cells without oral p retreatment of PTX, two out of five (40%) developed liver metastases. There was a slight, but not significant (P = 0.08) increase in both ex perimental and spontaneous lung metastases formation in PTX-treated an imals, However, tumor nodule formation on the lung surface was ineffic ient. PTX also increased membrane fluidity of the Neuro2a cells and si gnificantly decreased tumor cell adhesion to fibronectin-coated microt iter wells (P < 0.01), We conclude that PTX has a cytostatic effect on the Neuro2a mouse neuroblastoma and exerts an anti-tumor effect on li ver metastases following intravenous administration of neuroblastoma c ells, Whether these results are directly related to the changes in mem brane properties caused by pentoxifylline remains to be established.