Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Xu HZ, Dai LH, Zhang HR, et al. Zhengguangmycin A6 and its status in the complex of Zhengguangmycins[J]. Acta Pharma Sin 1988; 23: 667–71.
Jiang M, Zhen YS. Antitumor activity of bleomycin A6 against human liver cancer in cell culture and in nude mice[J]. Acta Pharm Sin 1987; 22: 881–5.
Deng YC, Zhen YS, Zheng S, et al. Inhibitory effect of bleomycin A6 on human colon cancer xenogratts in nude mice(in Chinese)[J]. Acta Acad Med Sin 1990; 12: 335–40.
Liu XJ, Li Y, Zhen YS. Inhibitory effect of boanmycin on the growth of colon carcinoma and hepatic metastasis in mice[J]. Acta Pharm Sin 2001; 36: 14–8.
Zhen YX, Hosokawa M, Morikawa K, et al. Enhanced susceptibility of target KMT-17 cells to activated macrophages by treatment with the antitumor agent bleomycin[J]. Cancer Immunol Immunother 1986; 23: 46–50.
Mantovani A, Bottazzi B, Sozzani S, et al. Cytokine regulation of tumor-associated macrophages[J]. Res Immunol 1993; 144: 280–3.
Opdenakker G, Van Damme J. Chemotactic factors, passive invasion and metastasis of cancer cells[J]. Immunol Today 1992; 13: 463–4.
Wang JM, Chertov O, Proost P, et al. Purification and identification of chemokines potentially involved in kidney-specific metastasis by a murine lymphoma variant: induction of migration and NFκB activation[J]. Int J Cancer 1998; 75: 900–7.
Nast CC, LeDUC LE. Chemotactic peptides mechanism, functions and possible role in inflammatory bowel disease[J]. Dig Dis Sci 1988; 33: 50s-57s.
Daughaday CC, Mehta J, Spilberg I, et al. Deactivation of guinea pig pulmonary alveolar macrophage responses to N- formyl- methionyl- leucyl- phenyl- phenylalanine: chemotaxis, superoxide generation and binding[J]. J Immunol 1985; 134: 1823–6.
Cao SS and Zhen YS. Potentiation of antimetabolite antitumor activity in vivo by dipyrida mole and amphotericin B[J]. Cacner Chemother Pharmacol 1989; 24: 181–6.
Zhong M, Cheng GF, Lai CN, et al. Effecdts of isorhapotigenin and resveratrol on interleukin 6 mRNA expression from stimulated peritoneal macrophages of mice[J]. Acta Pharm Sin 1999; 34: 329–32.
Leiper K, Campbell BJ, Jenkinson MD, et al. Interaction between bacterial peptides, neutrophils and goblet cells: a possible mechanism for neutrophil recruitment and goblet cell depletion in colitis[J]. Lin Sci (Lond), 2001; 101: 395–402.
Zhang L, Khayat A, Cheng HS, et al. The pattern of monocyte recruitment in tumors is modulated by MCP-1 expression and influences the rate of tumor growth[J]. Lab Invest 1997; 76: 579–90.
Morikawa K, Nayar R, Fidler I. In vitro activation of tumoricidal properties in mouse macrophages using the chemotactic peptide N- formyl- methionyl- leucyl-phenylalanine (FMLP) incorporated in liposimes[J]. Cancer Immunol Immunother 1988; 27: 1–6.
Author information
Authors and Affiliations
Corresponding author
Additional information
Foundation item: This work was supported by the “973” Major State Basic Research Project of china (No. G1998051104)
Biography: LI Zhong-dong(1965–), male, doctor of medicine, associate professor, General Hospital of Air Force, PLA, majors in clinical pharmacy.
Rights and permissions
About this article
Cite this article
Li, Zd., Li, Y. & Zhen, Ys. Potentiation of boanmycin antitumor activity by chemotactic peptide. Chin. J. Cancer Res. 17, 79–83 (2005). https://doi.org/10.1007/s11670-005-0048-8
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11670-005-0048-8