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Interaction of endotoxin and polymyxin B in B16 mouse melanoma model of metatstasis

Katarzyna Kempińska ,  Beata Filip-Psurska ,  Magdalena Milczarek ,  Joanna Wietrzyk ,  Elżbieta Piasecka-Pajtasz ,  Czesław Ługowski ,  Janusz Boratyński 

Polish Academy of Sciences, Institute of Immunology and Experimental Therapy (IITD), Rudolfa Weigla 12, Wrocław 53-114, Poland


Lipopolysacharides (LPS) has been recognized as an efficient immune stimulator as well as multicytokine inducer and it is believed to have a potent antitumor and antimetastatic activity through a host-defense mechanism. So far it has been demonstrated that LPS could regress tumor growth in animal cancer models, which occurs to be promising even for cancer immunotherapy in humans. However, its use in human cancer therapy has been limited only to one trial, since is toxic causing sepsis.

Numerous peptides have been designed to bind and neutralize LPS. One of them is a natural peptide polymyxin B (PMB) which prevents noxious LPS effects occurrence during LPS-mediated endotoxin shock in animal models. The Polymyxin B mechanism of action depends on its interactions with bacterial cell membrane phospholipids what results in disruption of membrane structure.

In order to obtain the anticancer effect of LPS avoiding its toxicity we investigated the influence of LPS complexes with polymyxin and LPS complexes with anti-LPS antibody on lung metastases formation in the mice bearing B16 melanoma. In mice treated with LPS and  polymyxin the number of metastatic foci was approximately 50-70% lower in comparison to control group of mice. We didn’t observed antimetastatic effect in mice treated with LPS alone. Treatment with polymyxin alone showed stimulation of metastatic foci formation.

This work was partly supported by Polish Ministry of Science and Higher Education -The National Centre for Research and Development (NCBiR) NR 13 0089 06 “Products of cell lysis of Gram negative bacteria”


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Submitted: 2012-03-15 10:38
Revised:   2012-03-19 10:07