摘要
Objective: Chemotactic peptide may interfere with the process of tumor growth, invasion and metastasis by activating and attracting leukocytes containing macrophages. fMLP (CHO-Met-II e-Phe) is one of the chemotactic peptides. Boanmycin (BAM), a single A6 component from the bleomycin complex, is effective against a panel of cancers in clinical trials. This study was set to investigate the antitumor activity of BAM in combination with chemotactic peptide fMLP. Methods: Cytotoxicity of BAM and fMLP to cancer cells was determined by MTT assay. Therapeutic effect was evaluated by using the model of subcutaneously transplanted hepatoma 22 in mice. Results were judged as that a CDI less than 0.85 was considered as synergism and one less than 0.75 as significant synergism. Results: BAM and fMLP showed no synergism in cytotoxicity to cancer cells. In all in vivo experiments, fMLP was administered peritumorally at the dose of 1 mg/mouse; no significant inhibition by fMLP alone on the growth of hepatoma 22 was found. Different settings of BAM and fMLP combination included: (1) BAM, administered peritumorally×3, was started 24 h after tumor inoculation. BAM (0.5 mg/kg) alone and BAM-fMLP combination inhibited the growth of hepatoma 22 by 26.6% and 64.7%, respectively (P<0.05, CDI=0.36) on day 13. (2) BAM, administered ip×3, was started 24 h after tumor inoculation. The growth of tumor in BAM (1 mg/kg) group was faster than that in BAM-fMLP combination group. On day 14, BAM (1 mg/kg) alone and BAM-fMLP combination suppressed the growth of tumor by 11% and 70.6%, respectively (P<0.05), CDI=0.42). (3) BAM, administered ip×3, was started 96 h after tumor inoculation. The growth of tumor in BAM (1 mg/kg) group was faster than that in BAM-fMLP combination group. On day 13, BAM (1 mg/kg) alone and BAM-fMLP combination suppressed tumor growth by 38.2% and 77.1%, respectively (P<0.05, CDI=0.51). As shown in all in vivo experimental settings, antitumor effect of BAM in combination with fMLP was much more potent than that of BAM alone. Conclusion: This experiment shows that chemotactic peptide fMLP may enhance the antitumor effect of BAM, which indicates that chemotactic modulation may play a positive role in cancer chemotherapy.
Objective: Chemotactic peptide may interfere with the process of tumor growth, invasion and metastasis by activating and attracting leukocytes containing macrophages. fMLP (CHO-Met-II e-Phe) is one of the chemotactic peptides. Boanmycin (BAM), a single A6 component from the bleomycin complex, is effective against a panel of cancers in clinical trials. This study was set to investigate the antitumor activity of BAM in combination with chemotactic peptide fMLP. Methods: Cytotoxicity of BAM and fMLP to cancer cells was determined by MTT assay. Therapeutic effect was evaluated by using the model of subcutaneously transplanted hepatoma 22 in mice. Results were judged as that a CDI less than 0.85 was considered as synergism and one less than 0.75 as significant synergism. Results: BAM and fMLP showed no synergism in cytotoxicity to cancer cells. In all in vivo experiments, fMLP was administered peritumorally at the dose of 1 mg/mouse; no significant inhibition by fMLP alone on the growth of hepatoma 22 was found. Different settings of BAM and fMLP combination included: (1) BAM, administered peritumorally×3, was started 24 h after tumor inoculation. BAM (0.5 mg/kg) alone and BAM-fMLP combination inhibited the growth of hepatoma 22 by 26.6% and 64.7%, respectively (P<0.05, CDI=0.36) on day 13. (2) BAM, administered ip×3, was started 24 h after tumor inoculation. The growth of tumor in BAM (1 mg/kg) group was faster than that in BAM-fMLP combination group. On day 14, BAM (1 mg/kg) alone and BAM-fMLP combination suppressed the growth of tumor by 11% and 70.6%, respectively (P<0.05), CDI=0.42). (3) BAM, administered ip×3, was started 96 h after tumor inoculation. The growth of tumor in BAM (1 mg/kg) group was faster than that in BAM-fMLP combination group. On day 13, BAM (1 mg/kg) alone and BAM-fMLP combination suppressed tumor growth by 38.2% and 77.1%, respectively (P<0.05, CDI=0.51). As shown in all in vivo experimental settings, antitumor effect of BAM in combination with fMLP was much more potent than that of BAM alone. Conclusion: This experiment shows that chemotactic peptide fMLP may enhance the antitumor effect of BAM, which indicates that chemotactic modulation may play a positive role in cancer chemotherapy.
基金
This work was supported by the "973" Major State Basic Research Project of china (No. G1998051104)
