Inducible NO synthase inhibits the growth of free tumor cells, but enhances the growth of solid tumors.

To elucidate the role of nitric oxide (NO) in tumor cell growth in vivo, dynamic aspects of the growth of Ehrlich ascites tumor cells (EATCs) were studied in wild-type (WT) mice and in an inducible strain of NO synthase (iNOS)-deficient (iNOS(-/-)) mice. Kinetic analysis showed that the rate of free tumor cell growth in the peritoneal cavity was significantly higher in the iNOS(-/-) mice than in the WT mice. In contrast, EATCs inoculated subcutaneously rapidly grew and formed a solid tumor in WT mice, but failed to grow in iNOS(-/-) mice. These results clearly indicate that NO generated by iNOS predominantly inhibits the growth of tumor cells in their free form, but enhances the growth of solid tumors.