title: Evaluation of a gemcitabine-doxorubicin-paclitaxel combination schedule through flow cytometry assessment of apoptosis extent induced in human breast cancer cell lines.
abstract: Combination chemotherapy with gemcitabine (Gem), doxorubicin (Dox), and paclitaxel (Pac) (GAT) has been considered attractive as first-line treatment in metastatic breast cancer. We compared the potential of various schedules of GAT to induce apoptosis on MDA-MB-231, MCF7, and T47D human breast cancer cell lines. The extent of apoptotic induction was analyzed by flow cytometry with 7-aminoactinomycin D (7AAD) staining. Differences between various schedules in terms of apoptotic induction were statistically significant (P < 0.05). The most effective apoptotic induction regimen was achieved by the sequence: Dox for 16 h followed by Pac + Gem. Schedules employing a 16-h interval between drug administrations induced higher levels of apoptosis in human breast cancer cell lines compared with schedules using a 4-h interval. The therapeutic efficacy of the experimental results shown in this paper has been clinically corroborated in a phase II trial in metastatic breast cancer patients.
authors.affiliation: Department of Health Sciences, Faculty of Experimental Sciences, University of Jaén, 23071-Jaén, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Serrano
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez-Rovira
authors.forename: Ignacio
authors.initials: I
authors.lastname: Algarra
authors.forename: Ana
authors.initials: A
authors.lastname: Jaén
authors.forename: Ana
authors.initials: A
authors.lastname: Lozano
authors.forename: José J
authors.initials: JJ
authors.lastname: Gaforio
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D002470:Cell Survival; D002986:Clinical Trials as Topic; D003609:Dactinomycin / Q000494:pharmacology; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D005434:Flow Cytometry; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D000903:Antibiotics, Antineoplastic; D003841:Deoxycytidine; D003609:Dactinomycin; D004317:Doxorubicin; D017239:Paclitaxel; D000093542:Gemcitabine