Complete inhibition of spontaneous pulmonary metastasis of human lung carcinoma cell line EBC-1 by a neutrophil elastase inhibitor (ONO-5046.Na).

We previously reported that EBC-1, a non-small cell lung cancer (NSCLC) cell line, produces immunoreactive neutrophil elastase (NE). In the present study, we examined the effects of ONO-5046.Na, a specific NE inhibitor, on the in vivo growth and spontaneous pulmonary metastasis of EBC-1 transplanted into severe combined immunodeficiency (scid) mice. In control mice, EBC-1 tumors inoculated subcutaneously grew steadily throughout 8-week observation period. The daily intraperitoneal injection of ONO-5046.Na (50 mg/kg/day) from day 1 completely suppressed the tumor growth. When ONO-5046.Na treatment was initiated 14 days after EBC-1 inoculation, it also caused a significant delayed growth of this cell line. Furthermore, ONO-5046.Na treatment completely inhibits the appearance of metastatic foci in lung at 8 weeks not only when it was administered from day 1 but also when treatment was initiated 14 days after tumor inoculation, when solid tumors started to grow. The weight of the mice treated with ONO-5046.Na was similar to that of the control mice at 8 weeks, and they appeared as healthy as the control mice during the treatment. These results indicated that a NE inhibitor, ONO-5046.Na, inhibited both primary and metastatic growth of NSCLC with no marked side effects.