| At present, antitumoral activity of chemotherapeutic drugs depends on not only tumor cell sensitivity, but also biological factors of host. We studied the biological modulation of antitumor activity of new antitumor antibiotics, boanmycin and lidamycin, by chemotactic modulation, antiadhesion or reduction of adverse drug reaction.Part I Antitumor activity of BAM-fMLP combinationBoanmycin (BAM) is A6 component of bleomycin, which is effective against a panel of tumors in clinical trial. Chemotactic peptides attract and activate leukocytes which interfere with tumor growth, invasion and metastasis. fMLP (CHO-Met-ILe-Phe) is one of chemotactic peptides. Antitumor action of BAM-fMLP combination was investigated in this experiment.Cytotoxicity of BAM-fMLP combination to tumor cells was determined by MTT assay in vitro, especially in the presence of macrophages. The results showed that BAM-fMLP combination has no synergistic effect on tumor cells, but BAM at the doses of 10 μ g/ml, 30 μ g/ml and 100 μ g/ml in combination with fMLP at the concentration 20 μ g/ml exhibited synergistic effect on tumor cells in the presence of macrophages.The mechanism that BAM-fMLP combination showed synergistic cytotoxicity to tumor cells was studied. The experiment was set on the basis that fMLP may stimulate macrophages to release superoxide anion (O2-), nitric oxide (NO) and interleukin-6 (IL-6) and so on. The amount of O2- released from fMLP stimulated macrophages was determined by NBT assay. The result showed that the amount of O2- released from fMLP (4.6×10-7 mol/L) stimulated macrophages which were treated by BAM in vitro increased significantly. Positive rate ascended from 24.4 ± 6.6 of control to 62.0 ± 9.4, 57.2±7.4 and 48.8±10 of those treated with BAM 1 μ g/ml,10μ g/ml and 100 μ g/ml, respectively (P<0.01). The amount of O2- released from fMLP (4.6×10-7 mol/L) stimulated macrophages that were collected from mice treated with BAM 1mg/kg, 3mg/kg and 10mg/kg in vivo was also increased markedly. Positive rate was increased from 20.0 ± 5.5 of control to 91.6±0.76 , 88.7 ± 3.3 and 84.0 ± 7.0 of those treated with BAM 1mg/kg, 3mg/kg and 10mg/kg., respectively (P<0.01).As known, nitric oxide (NO) became nitrite (NO2-) soon in vitro. The amount of NO2-determined by Griess method may represent that of NO indirectly. When murine... |
