Pharmacogenomic Approach for the Identification of Novel Determinants of Resistance to Oxaliplatin in Colon Cancer

ABSTRACT: Oxaliplatin is a member of the family of Pt-containing chemotherapeutic agents that also include cisplatin (CDDP) and carboplatin. OXA is distinguished from these two older drugs by its different spectrum of activity both in preclinical models and in clinical trials. It is the only platinum analogue to have activity in colon cancer, a disease for which this drug has now become a mainstay of therapy. It mainly forms intrastrand adducts between two adjacent guanine residues or guanine and adenine, disrupting DNA replication and transcription. OXA has been reported to be involved in the Nucleotide Excision Repair Pathway (NER), p38 kinase activation, PI3K/AKT pathway and caspases cascade activation through apoptotic intrinsic pathway. However, the downstream molecular events underlying the cytotoxic effects of this chemotherapeutic agent have not been well characterized. This study was developed in order to clarify the multifactoriality of the resistance acquisition process and to identify genes and pathways that could play a role as markers in OXA sensitivity. Keywords: Drug resistance The goal of our experiment was to determine a gene expression profile that discriminates between the OXA-sensitive colorectal cancer cell lines HT29, LoVo, DLD1 and LS513 group and the group of OXA-resistant derived cell lines HTOXAR3, LoVOXAR3, DLDOXAR3 and LSOXAR3 in order to clarify the multifactoriality of the resistance acquisition process and to identify genes and pathways that could play a role as markers in OXA sensitivity. The experimental design used was “RNA-Reference” and “Dye-Swap”. Each cell line was analyzed in duplicate, with RNA reference (Stratagene) as reference sample and labeled each biological condition once by Cy3 and once by Cy5. Taking the average of two arrays thus labeled, cancel the dye effect on any particular gene. In total we used 16 slides.

ORGANISM(S): Homo sapiens

SUBMITTER: Bandres Eva 

PROVIDER: E-GEOD-10405 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress