[Minocycline potentiates the antimetastatic effect of boanmycin].
Boanmycin (bleomycin A6, BAM) was found to markedly inhibit the spontaneous pulmonary metastasis of Lewis carcinoma in mice. Compared at equitoxic doses (1/9 LD50), BAM was more effective than mitomycin. Minocycline (MNO) at 5 mg.kg-1 showed no inhibition on the growth of sc transplanted Lewis primary tumor; however, it markedly potentiated the antimetastatic effect of BAM. Treated with BAM (5 mg.kg-1) alone, the number of total metastatic foci and that of large foci (> 2 mm 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 by 88% and 100%, respectively. By NAG enzyme assay, MNO was not cytotoxic and showed no synergism with BAM against PG cells, a cell line derived from a highly metastatic human giant cell carcinoma of the lung. Determined by ELISA with a monoclonal antibody, the expression of type IV collagenase in PG cells was remarkably inhibited by MNO. The intracellular free Ca2+ level in PG cells was reduced from 76.7 nmol.L-1 to 42.2 nmol.L-1 by MNO treatment. The study suggests that the combination of boanmycin and minocycline may be useful for control of tumor metastasis and the inhibition of type IV collagenase expression may be involved in the mechanism of minocycline potentiation.
Liu
J G
JG
Institute of Medicinal Biotechnology, Peking Union Medical College.
Jiang
M
M
Xu
L N
LN
Zhen
Y S
YS
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018286:Carcinoma, Giant Cell / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000556:secondary*; D004357:Drug Synergism; D005260:Female; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; C052656:bleomycin A6; D001761:Bleomycin; D008911:Minocycline