[Chemotactic peptide fMLP enhances antitumor activity of boanmycin].
OBJECTIVE
Boanmycin (BAM), a single A6 component of the bleomycin complex, is effective against a panel of cancers in clinical trials. Chemotactic peptide can activate and attract leukocytes and macrophages that may interfere with the process of tumor growth, invasion, and metastasis. This study was designed to investigate the antitumor activity of BAM in combination with chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine(fMLP).


METHODS
Cytotoxicity of BAM and fMLP to tumor cells was determined by MTT assay, particularly in presence of macrophages. Therapeutic effect was evaluated by using the model of subcutaneously transplanted hepatoma 22 in mice.


RESULTS
In vitro experiment showed that BAM and fMLP had no synergism in cytotoxicity to tumor cells. However, in the presence of macrophages, BAM at concentrations of 10, 30, and 100 micrograms/ml in combination with fMLP 20 micrograms/ml displayed synergistic effect in cytotoxicity. In all in vivo experiments, fMLP administered peritumorally 3 times at the dose of 1 mg/mouse showed no significant growth inhibition. Three settings of BAM and fMLP combination included: (1) BAM, administered peritumorally x 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 i.p. x 3, was started 24 h after tumor inoculation. The tumor growth 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 tumor growth by 11% and 70.6%, respectively (P < 0.05, CDI = 0.42). (3) BAM, administered i.p. x 3, was started 96 h after tumor inoculation. The tumor growth 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 the 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.


CONCLUSIONS
This experiment shows that chemotactic peptide fMLP may enhance the antitumor effect of BAM and the enhancement may need the participation of macrophages. Chemotactic modulation may play a role in cancer chemotherapy.
Li
Zhong-dong
ZD
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, P. R. China.
Li
Yi
Y
Zhen
Yong-su
YS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; C052656:bleomycin A6; D001761:Bleomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine