title: BCRP and P-gp relay overexpression in triple negative basal-like breast cancer cell line: a prospective role in resistance to Olaparib.
abstract: The triple negative basal-like (TNBL) breast carcinoma is an aggressive and unfavorable prognosis disease. Inhibitors of poly(ADP-ribose) polymerase such as Olaparib could represent a promising targeted therapy but their sensitivity against Multidrug Resistance proteins (MDR), which causes resistance, is not well defined. Thus, our work focused on the analysis of P-gp and BCRP coexpression in the SUM1315 TNBL human cell line, in correlation with Olaparib intracellular concentration. Western blot analyses showed a clear coexpression of P-gp and BCRP in SUM1315 cells. A low cytotoxic Olaparib treatment clearly led to an increased expression of both BCRP and P-gp in these cells. Indeed, after 1.5 h of treatment, BCRP expression was increased with a 1.8 fold increase rate. Then, P-gp took over from 3 h to 15 h with an average increase rate of 1.8 fold, and finally returned to control value at 24 h. HPLC-UV analyses showed that, in the same treatment conditions, the intracellular Olaparib concentration increased from 1 h to 3 h and remained relatively stable until 24 h. Results suggest that the resistance mechanism induced by Olaparib in TNBL SUM1315 cell line may be overpassed if a cytotoxic and stable intracellular level of the drug can be maintained.
authors.affiliation: 1] Clermont Université - Université d'Auvergne - ERTICa - EA 4677 - Institut Universitaire de Technologie, Département Génie Biologique, Ensemble universitaire des Cézeaux, B.P. 86 - 63172 AUBIERE CEDEX, France [2] Clermont Université - Université d'Auvergne - ERTICa - EA 4677. Centre Jean Perrin, 58 Rue Montalembert, BP 392 - 63011 CLERMONT-FERRAND CEDEX France.
authors.forename: Robin
authors.initials: R
authors.lastname: Dufour
authors.affiliation: Clermont Université - Université d'Auvergne - ERTICa - EA 4677 - Institut Universitaire de Technologie, Département Génie Biologique, Ensemble universitaire des Cézeaux, B.P. 86 - 63172 AUBIERE CEDEX, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Daumar
authors.affiliation: UMR 990 INSERM - Université d'Auvergne, BP 184, 63005 CLERMONT-FERRAND CEDEX, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mounetou
authors.affiliation: Clermont Université - Université d'Auvergne - ERTICa - EA 4677. Faculté de médecine, 28 place Henri Dunant, BP 38 - 63001 Clermont-Ferrand, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Aubel
authors.affiliation: Clermont Université - Université d'Auvergne - ERTICa - EA 4677. Centre Jean Perrin, 58 Rue Montalembert, BP 392 - 63011 CLERMONT-FERRAND CEDEX France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Kwiatkowski
authors.affiliation: Clermont Université - Université d'Auvergne - ERTICa - EA 4677. Centre Jean Perrin, 58 Rue Montalembert, BP 392 - 63011 CLERMONT-FERRAND CEDEX France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Abrial
authors.affiliation: Clermont Université - Université d'Auvergne - ERTICa - EA 4677 - Institut Universitaire de Technologie, Département Génie Biologique, Ensemble universitaire des Cézeaux, B.P. 86 - 63172 AUBIERE CEDEX, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vatoux
authors.affiliation: Clermont Université - Université d'Auvergne - ERTICa - EA 4677. Centre Jean Perrin, 58 Rue Montalembert, BP 392 - 63011 CLERMONT-FERRAND CEDEX France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Penault-Llorca
authors.affiliation: Clermont Université - Université d'Auvergne - ERTICa - EA 4677 - Institut Universitaire de Technologie, Département Génie Biologique, Ensemble universitaire des Cézeaux, B.P. 86 - 63172 AUBIERE CEDEX, France.
authors.forename: Mahchid
authors.initials: M
authors.lastname: Bamdad
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010793:Phthalazines / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C531550:olaparib