MOLECULAR MECHANISMS OF ACTION AND PREDICTION OF RESPONSE TO OXALIPLATIN IN COLORECTAL CANCER CELLS

Summary In our study we investigated the contribution of ox aliplatin to mediated toxicity and transcription profile of genes involves in cancer i n order to understand the mechanisms involved in tumor cell apoptosis and cancer disease progression. As colorectal cancer model we used the Colo320 cell line. We evaluated t he oxaliplatin induced toxicity of a single dose of different concentrations at 24, 48 a nd 72 hours, and also multiple doses at different times, in order to establish the IC 50 concentration. p53, NF B and PDGF gene expression levels were evaluated after treatment wi th a concentration close to the IC 50 using the RT-PCR technique. The purpose of the study is to observe the changes in pharmacokinetic parameters after administration of a single dose in order to establish IC 50 , using the MTT cell proliferation assay on the lin e Colo320. We compared the parameters of cell proliferation observed after adm inistration of a single dose and multiple doses, and tried to establish an optimal t ime and frequency of oxaliplatin treatment that induces the minimal cytotoxic effect . After evaluating the modulation of gene expression after treatment with oxaliplatin, w e obtained a high gene expression of two major pro-apoptotic genes, p53 and NF B (nuclear factor-B) and the inhibition of a pro-angiogenic factor, the platelet-derived growt h factor (PDGF). In conclusion, the frequency of drug administration is important, and may establish the minimum dose required and the frequency of administration, with maximum biological results and without adverse effect.