title: Adriamycin in combination with dexamethasone and octreotide lacks activity on the treatment of a 4T1 metastatic breast cancer model.
abstract: The aim of this study was to evaluate whether the palliative treatment for metastatic disease with dexamethasone (DEX) plus octreotide (OCT) can improve the anticancer effects of the standard treatment with adriamycin (ADR) on a 4T1 metastatic breast cancer (MBC) model. 4T1 cells were first characterized for the expression of the somatostatin receptors 1-5 and were then inoculated onto the femur of BALB/C mice. Investigation protocols used 4T1 cell proliferation and invasion assays, analysis of radiographic images of the bone metastatic lesions, and overall survival of the diseased animals. The triple combination treatment regime (ADR+OCT+DEX) was ineffective for growth inhibition and showed an antagonistic effect on ADR activity in the 4T1 cell line in both proliferation and invasion assays. ADR treatment following the administration of the DEX+OCT regimen decreased the anticancer activity of ADR both on the grading of the bone metastatic lesions and on the overall survival of diseased animals. Moreover, the palliation treatment with OCT+DEX and in combination with ADR rather caused disease progression of the metastatic disease and bone lesions in a 4T1 MBC model in vivo. These results suggest that the administration of the DEX+OCT regimen, although may preserve palliative effects, neutralizes or reverses the anticancer effects of ADR on a 4T1 MBC model in vitro and in vivo. The simultaneous use of these drugs should be considered carefully in clinical practice.
authors.affiliation: aLaboratory of Pharmacology bDepartment of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Athens cLaboratory of Cell Culture, Molecular Modeling and Drug Design dLaboratory of Experimental Chemotherapy, Symeonidion Research Center eDepartment of Radiology, Theagenion Cancer Hospital, Thessaloniki, Greece.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Dalezis
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Trafalis
authors.forename: George D
authors.initials: GD
authors.lastname: Geromichalos
authors.forename: Nikos
authors.initials: N
authors.lastname: Pissimissis
authors.forename: Dimitra
authors.initials: D
authors.lastname: Panagiotopoulou
authors.forename: Grammati
authors.initials: G
authors.lastname: Galaktidou
authors.forename: Efi
authors.initials: E
authors.lastname: Papageorgiou
authors.forename: Athanassios
authors.initials: A
authors.lastname: Papageorgiou
authors.forename: Maria
authors.initials: M
authors.lastname: Lymperi
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology; D011897:Random Allocation; D017481:Receptors, Somatostatin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D017481:Receptors, Somatostatin; D003907:Dexamethasone; D004317:Doxorubicin; D015282:Octreotide