A proteomic kinetic analysis of IGROV1 ovarian carcinoma cell line response to cisplatin treatment.
Ovarian cancer is one of the leading causes of mortality by gynecological cancer. Despite good response to surgery and initial chemotherapy, essentially based on cisplatin (cis-diamino-dichloro-platinum(II) (CDDP)) compounds, frequent recurrences with chemoresistance acquisition are responsible for poor prognosis. Several mechanisms have been described as implicated in CDDP resistance, however they are not sufficient to exhaustively account for this resistance emergence. We applied a proteomic approach based on 2-DE coupled with MS (MALDI-TOF/TOF) to identify proteins associated with chemoresistance induced by CDDP. A kinetic analysis of IGROV1 cell behavior following treatment with CDDP and subsequent statistical analysis revealed time and/or concentration-dependent modifications in protein expression. We evidenced events such as decreased amino-acid and nucleotide synthesis potentially associated with cell cycle blockade, and variations that may be related to resistance acquisition, such as possible enhanced glycolysis and increased proliferating potential. Moreover, overexpressions of aldehyde dehydrogenase 1 and both cytokeratins 8 and 18 were consistent with our previous findings, demonstrating that expression of these proteins was increased in cisplatin-resistant IGROV1-R10 as compared to IGROV1 parental cells. Identification of such proteins could allow improved understanding of the mechanisms leading to cell death or survival and, thus, to the acquisition of chemoresistance.
Le Moguen
Karen
K
Groupe Régional d'Etudes sur le Cancer - EA 1772 (Université de Caen-Basse Normandie), Unité Biologie et Thérapies Innovantes des Cancers Localement Agressifs, Centre de Lutte Contre le Cancer François Baclesse, Caen, France. k.le.moguen@baclesse.fr
Lincet
Hubert
H
Marcelo
Paulo
P
Lemoisson
Edwige
E
Heutte
Natacha
N
Duval
Marilyne
M
Poulain
Laurent
L
Vinh
Joëlle
J
Gauduchon
Pascal
P
Baudin
Bruno
B
D000230:Adenocarcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000032:analysis / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D040901:Proteomics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D002945:Cisplatin