RESUMO
PURPOSE: Metformin has been widely used for the treatment of Type 2 Diabetes Mellitus (T2DM), hyperglycemia and polycystic ovarian syndrome. Recent studies have suggested the potential of this substance as a cancer chemopreventive agent. We evaluated the antitumoral effect of iRNA-PFK-1 and the combined therapy iRNA-PFK-1 + metformin in RKO p53-positive cells. METHODS: mRNA levels of tumor suppressor genes AMPK, APC, and c-MYC, KRAS oncogenes were measured by qRT-PCR in RKO cells treated with 25 µM metformin alone or combined with iRNA-PFK-1, to evaluate the effect of both treatments. RESULTS: At 72 h after treatment with either 25 µM metformin, 150 nM iRNA-PFK-1, or the combined treatment, the transcriptional levels of these biomarkers were decreased by ~73% (pË0.05), ~99.9%, (pË0.01), and ~76% (pË0.05), respectively. CONCLUSION: These in vitro results support the potential therapeutic role of metformin and PFK-1 in the treatment of colon cancer via down-modulation of the expression of several important cancer biomarkers.
Assuntos
Biomarcadores Tumorais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Regulação para Baixo/efeitos dos fármacos , Metformina/administração & dosagem , Fosfofrutoquinase-1/administração & dosagem , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Combinação de Medicamentos , Humanos , Fosfofrutoquinase-1/genética , RNA , Células Tumorais CultivadasRESUMO
The aim of this study was to investigate the relationship between functional polymorphisms Gly482Ser in PPARGC1A and Pro12Ala in PPARG2 with the presence of obesity and metabolic risk factors. We included 375 individuals characterized as Mexican-Mestizos and classified by the body mass index (BMI). Body dimensions and distribution of body fat were measured. The HOMA-IR and adiposity indexes were calculated. Adipokines and metabolic profile quantification were performed by ELISA and routine methods. Genetic polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism analysis. A difference between obese and nonobese subjects in polymorphism PPARGC1A distribution was observed. Among obese individuals, carriers of genotype 482Gly/Gly were observed to have decreased body fat, BMI, and body fat ratio versus 482Ser/Ser carriers and increased resistin and leptin levels in carriers Gly+ phenotype versus Gly- phenotype. Subjects with PPARG2 Ala- phenotype (genotype 12Pro/Pro) showed a decreased HOMA-IR index versus individuals with Ala+ phenotype (genotypes 12Pro/Ala plus 12Ala/Ala). We propose that, in obese Mexican-Mestizos, the combination of alleles 482Ser in PPARGC1A and 12Pro in PPARG2 represents a reduced metabolic risk profile, even when the adiposity indexes are increased.