Sequence-dependent synergism and antagonism between paclitaxel and gemcitabine in breast cancer cells: The importance of scheduling
| العنوان: | Sequence-dependent synergism and antagonism between paclitaxel and gemcitabine in breast cancer cells: The importance of scheduling |
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| المؤلفون: | Rafael de Llorens, Joan Brunet, Javier A. Menendez, Ramon Colomer, Alejandro Vazquez-Martin, Cristina Oliveras-Ferraros |
| المصدر: | Europe PubMed Central © International Journal of Oncology, 2008, vol. 32, núm. 1, p. 113-120 Articles publicats (D-B) DUGiDocs – Universitat de Girona instname Recercat. Dipósit de la Recerca de Catalunya Scopus-Elsevier |
| بيانات النشر: | Spandidos Publications, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Cancer Research, medicine.medical_specialty, Paclitaxel, endocrine system diseases, Antineoplastic Agents, Apoptosis, Breast Neoplasms, Deoxycytidine, Drug Administration Schedule, Medicaments antineoplàstics, chemistry.chemical_compound, Cell Line, Tumor, Internal medicine, Antineoplastic agents, medicine, Humans, Breast -- Cancer, Viability assay, business.industry, Cancer, Drug Synergism, Cell cycle, medicine.disease, Gemcitabine, Endocrinology, Oncology, chemistry, SKBR3, Cancer cell, Mama -- Càncer, Cancer research, Female, Poly(ADP-ribose) Polymerases, business, medicine.drug |
| الوصف: | The marked clinical anticancer activity of the paclitaxel (PTX) and gemcitabine (GEM) combination has suggested that the two drugs may interact more than additively. We have analyzed the in vitro growth and molecular interactions of the two chemotherapy drugs in a panel of human breast cancer cells. We evaluated cell viability in four breast cancer cell lines (i.e., MCF-7, MDA-MB-231, MDA-MB-468, and SKBR3) that were treated with PTX and GEM combined either simultaneously (PTX + GEM) or sequentially (PTX --> GEM; GEM --> PTX). PTX-GEM interactions at the cellular level were assessed mathematically employing both the isobologram analysis (Berenbaum) and the combination index (Chou-Talalay) method. PTX-GEM molecular interactions on the apoptotic markers PARP, Bcl-2 and Bax were analyzed by immunoblotting procedures. Apoptosis was detected using a DNA ladder assay. We observed significant synergistic growth inhibitory interactions when PTX was administered before GEM. Additive interactions were observed when both the simultaneous regimen and the GEM followed by PTX regimen were used. DNA ladder and Western blotting results in the PTX followed by GEM sequence revealed a significant increase in the apoptotic cell death of breast cancer cells related to the Bax/Bcl-2 apoptotic pathway. In summary, the occurrence of clinically relevant synergism between PTX and GEM suggests a sequence-dependent nature in human breast cancer cells. This synergistic interaction on the PTXright curved arrow GEM schedule appears to be related to an increase in the Bcl-2-related mitochondrial apoptotic pathway. The synergism that we have observed may explain the favorable clinical responses that have been achieved in clinical studies, in which patients are administered PTX first, and then GEM. |
| وصف الملف: | application/pdf |
| تدمد: | 1791-2423 1019-6439 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c25db449259fadf9e1153dce04bb9e2Test https://doi.org/10.3892/ijo.32.1.113Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2c25db449259fadf9e1153dce04bb9e2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17912423 10196439 |
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