Abstract
Background and Objectives: Because of disadvantages of routine cancer therapies such as chemotherapy and radiotherapy, different microbial metabolites such as enterotoxins, bacterial proteins, recombinant toxins, and combination therapies have been used recently in treatment of cancers. Antitumor effects of verotoxin1 have been known from several years ago, that produced from some kinds of Escherichia coli. Our purpose was to study the synergistic cytotoxicity of verotoxin1 and monophosphoryl lipidA(MPL, a nontoxic derivative of bacterial lipopolysaccharide with adjuvant and tumor necrosing properties) on induced fibrosarcoma of Balb/c.
Methods and Methods: For animal experiments lethal dose 50 percent(LD50) calculated with Reed & Munch method by ten fold dilutions of verotoxin1 in different groups(5 mice in each group). Then intradermal tumors(mean diameter of 0/7-1 centimeter) induced with WEHI-164(3*106 cells in each mice) cells on back of animals, and divided in four groups. Group 4 used as control(heat inactivated verotoxin1, and groups 1,2 and 3 injected with verotoxin1(25 ng), MPL(50 mg), and combonations of MPL(25mg) and verotoxin1(25ng) respectively. After treatment, eradication or decrease in volume of tumors monitored daily and compared in 4 groups with ANOVA.
Results: verotoxin1 like standard vero cell line indicated cytotoxicity on WEHI-164 line in in vitro experiments. Simultaneouse treatment of tumors with verotoxin1 & MPL eradicated malignant fibrosarcoms of balb/c. 100 ng of verotoxin1 calculated as LD50 in Balb/c. Tumors injected with MPL indicated a little increase(not significant P>0/05) in volume in comparison with controls. Although animals of control group died after severe weight loss.
Conclusion: Our results indicated that verotoxin1 have synergistic effects with MPL in eradication of malignant fibrosarcomas of Balb/c. After further studies, it can be used for treatment of different tumors. Application of tow microbial metabolite as a treatment of tumors proposed and studied in this study.