Abstract:
Boanmycin(bleomycin A6, BAM)was found to markedly inhibit the spontaneouspulmonary metastasis of Lewis carcinoma in mice.Compared at equitowic doses (1/9 LD
50),BAMwas more effective than mitomycin。Minocycline (MNO)at 5 mg·kg
-1 showed no inhibition on thegrowth of sc transplanted Lewis primary tumor; however, it markedly potentiated the antimetastaticeffect of BAM. Treated with BAM(5 mg· kg
-1) alone,the number of total metastatic foci and thatof large foci (>2mm in diameter)in the lung were suppressed by 67%and 85%,respectively.When BAM was used in combination with MNO, the number of those foci was further reduced by88%and 100%, respectively.By NAG enzyme assay, MNO was not cytotoxic and showed nosynergism with BAM against PG cells, a cell line derived from a hlghly metastatic human giant cellcarcinoma of the lung.Determined by ELISA with a monoclonal antiboody,the expression of type IVcollagenase in PG cells was remarkably inhibited by MNO.The intracellular free Ca
2+ level in PGcells was reduced from 76.7 nmol·L
-1 to 42.2 nmol·L
-1 by MNO treatment. The study suggeststhat the combination of boanmycin and minocycline may be useful for control of tumor metastasis andthe inhibition of type IV collagenase expression may be involved in the mechanism of minocyclinepotentiation.