Original Article
Synergistic Action of fMLP-boanmycin Combination on the Growth of Mouse Colon Carcinoma and Its Action Mechanisms
Abstract
Objective: The inhibitory action of fMLP-boanmycin (BAM) combination on the growth of mouse colon carcinoma and its action mechanisms were observed in order to provide experimental proof for probing novel regimen of chemotactic modulation in combination with chemotherapy in the treatment of cancer.
Methods: Cytotoxicity of BAM-fMLP combination to tumor cells was determined by MTT assay in vitro. Antitumor activity of BAM-fMLP combination was assessed in mice subcutaneously transplanted colon carcinoma 26. The amount of superoxide anion (O2‧) released from fMLP stimulated macrophages was determined by NBT assay. The amount of nitric oxide (NO) was indirectly determined by Griess method.
Results:BAM-fMLP combination had no synergistic effect on tumor cells(CDI>0.85), but BAM at the doses of 10μg/ml, 30μg/ml and 100μg/ml in combination with fMLP at the concentration 20μg / ml exhibited synergistic effect on tumor cells in the presence of macrophages(CDI<0.75). fMLP inhibited the growth of colon carcinoma 26 by 50.0% when it at dose of 1 mg/mouse was administered peritumorally. BAM (1 mg/kg, intraperitoneally, three times) alone and BAM - fMLP combination inhibited the growth of colon carcinoma 26 by 38.6% and 78.4%, respectively (CDI=0.71) on day 12. The amount of O2‧ released from fMLP 4.6×10-7 mol/L (0.2μg/ml) stimulated macrophages which were treated by BAM in vitro increased significantly(P<0.01). fMLP 2.3×10-6 mol/L (1μg/ml) could not stimulate macrophages to release NO, but may stimulate macrophages treated with BAM 10μg/ml and 100μg/ml to release NO significantly(P<0.01).
Conclusion: The inhibitory action of fMLP-boanmycin combination on the growth of mouse colon carcinoma have synergism, which may associate with the increase of O2‧ and NO released by macrophages. Chemotactic modulation in combination with chemotherapy may be a novel regimen in the treatment of cancer.
Methods: Cytotoxicity of BAM-fMLP combination to tumor cells was determined by MTT assay in vitro. Antitumor activity of BAM-fMLP combination was assessed in mice subcutaneously transplanted colon carcinoma 26. The amount of superoxide anion (O2‧) released from fMLP stimulated macrophages was determined by NBT assay. The amount of nitric oxide (NO) was indirectly determined by Griess method.
Results:BAM-fMLP combination had no synergistic effect on tumor cells(CDI>0.85), but BAM at the doses of 10μg/ml, 30μg/ml and 100μg/ml in combination with fMLP at the concentration 20μg / ml exhibited synergistic effect on tumor cells in the presence of macrophages(CDI<0.75). fMLP inhibited the growth of colon carcinoma 26 by 50.0% when it at dose of 1 mg/mouse was administered peritumorally. BAM (1 mg/kg, intraperitoneally, three times) alone and BAM - fMLP combination inhibited the growth of colon carcinoma 26 by 38.6% and 78.4%, respectively (CDI=0.71) on day 12. The amount of O2‧ released from fMLP 4.6×10-7 mol/L (0.2μg/ml) stimulated macrophages which were treated by BAM in vitro increased significantly(P<0.01). fMLP 2.3×10-6 mol/L (1μg/ml) could not stimulate macrophages to release NO, but may stimulate macrophages treated with BAM 10μg/ml and 100μg/ml to release NO significantly(P<0.01).
Conclusion: The inhibitory action of fMLP-boanmycin combination on the growth of mouse colon carcinoma have synergism, which may associate with the increase of O2‧ and NO released by macrophages. Chemotactic modulation in combination with chemotherapy may be a novel regimen in the treatment of cancer.
