COMPLETE INHIBITION OF SPONTANEOUS PULMONARY METASTASIS OF HUMAN LUNG-CARCINOMA CELL-LINE EBC-1 BY A NEUTROPHIL ELASTASE INHIBITOR (ONO-5046-CENTER-DOT-NA)

We previously reported that EBC-1, a non-small cell lung cancel (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) mi ce. In control mice, EBC-1 tumors inoculated subcutaneously gr ew stea dily throughout 8-week observation period. The daily intraperitoneal i njection of ONO-5046 . Na (50 mg/kg/day) from day 1 completely suppres sed the tumor growth. When ONO-5046 . Na treatment was initiated 14 da ys after EBC-1 inoculation it also caused a significant delayed growth of this cell line. Furthermore, ONO-5046 . Na treatment completely in hibits the appearance of metastatic foci in lung at 8 weeks not only w hen if was administered from day 1 but also when treatment was initiat ed 14 days after tumor inoculation, when solid turners started to grow . The weight of the mice treated with ONO-5046 . Na was similar to tha t 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 in hibitor, ONO-5046 . Na, inhibited both primary and metastatic growth o f NSCLC with no marked side effects.