Administration of liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) and diclofenac in the combination attenuates their anti-tumor activities.
Abstract:
The anti-tumor effects of i.p. administered cyclooxygenase inhibitor - diclofenac and i.v. administered liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) were investigated using a s.c. growing murine fibrosarcoma tumor. Tumor growth was assessed by measuring tumor volumes and survival of the mice. Both of the drugs were administered either alone or in combination. Repeated application of diclofenac in two schedules (150 microg/mouse/day for 14 consecutive days or 2 x 150 microg/mouse/week for 4 weeks) or application of liposomal MTP-PE (2 x 20 microg/mouse/week for 4 weeks) starting on day 5 after tumor cell transplantation significantly suppressed the tumor growth and increased the percentage of surviving mice. However, the volume of tumors and the survival time in tumor bearing mice treated with the two agents were similar to untreated counterparts. Thus, these data suggest the anti-tumor activity of either of the two drugs is lost when they are used in combination. Hematological examinations confirmed previously observed hematopoiesis-stimulating activities of the drugs when given alone. However, mutually potentiating effects after combined administration of liposomal MTP-PE and diclofenac were observed only exceptionally. Our findings corroborate the recommendation that the interactions of drugs used for the treatment of tumors must be carefully checked, if the drugs are applied in combination.