Pharmacologically targeting tribbles gene expression in colorectal cancer

Abstract

Abstract Background TRIB1, TRIB2 and TRIB3 belong to the mammalian Tribbles family of pseudokinases proteins. Several studies reported Tribbles oncogenic role in different types of cancer, including colorectal cancer (CRC). Though current CRC treatment can be curative, patients are in risk of disease recurrence, meaning novel pharmacological targets and strategies are required. Our goal was to analyze Tribbles gene expression in CRC in response to different drugs. Methods Tribbles transcript levels were obtained from GEO profiles database (NCBI). Gene data sets (GDS) were selected based on experimental drug treatment description. Statistical analysis was performed at GraphPadPrism. Results Compared to non-treated control, TRIB2 expression was ∼2-fold increased in colorectal adenocarcinoma samples from patients treated with cyclooxygenase-2 inhibitor celecoxib (GDS3384), though not statistically significant (P < 0.1). TRIB1 was unaltered and data for TRIB3 was not available. By contrast, all Tribbles showed differential expression after treatment of SW620 colon cancer cells with supercritical rosemary extract in progressive increasing doses (0, 30, 60, 100 μg/mL) (P < 0.01;GDS5416). While both TRIB1 and TRIB3 were moderately increased in a dose-dependent manner (∼18% and 13%, respectively), TRIB2 was maximally down-regulated by ∼15% after 60 μg/mL. Conclusions Although celecoxib exhibits antiproliferative effects in different cancer cell types, TRIB2 gene expression showed a trend to be induced after treatment, in contrast to several genes involved in fatty acid oxidation that were down-regulated, which could result from a compensatory mechanism based on a metabolic shift. Since TRIB1/TRIB3 and TRIB2 were oppositely modulated in response to rosemary extract, additional studies are needed to validate its specific pharmacological potential interest for CRC treatment.