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Adriamycin in combination with dexamethasone and octreotide lacks activity on the treatment of a 4T1 metastatic breast cancer model

Dalezis, Panayiotis; Trafalis, Dimitrios T.; Geromichalos, George D.; Pissimissis, Nikos; Panagiotopoulou, Dimitra; Galaktidou, Grammati; Papageorgiou, Efi; Papageorgiou, Athanassios; Lymperi, Maria; Koutsilieris, Michael

doi: 10.1097/CAD.0000000000000484
PRECLINICAL REPORTS
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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.

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

Correspondence to Dimitrios Trafalis, MD, PhD, Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 75 Micras Asias, 115 27-Goudi, Athens, Greece Tel: +30 210 746 2587; fax: +30 210 746 2504; e-mail: pdalezis@med.uoa.gr

Received August 27, 2016

Accepted January 9, 2017

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