Curcumin reverses irinotecan-acquired resistance in colorectal cancer cells: insights from whole transcriptomic data

To investigate the key mechanisms underlying the acquisition of irinotecan resistance in colorectal cancer cells and the reversal of this resistance by curcumin, we utilized whole-genome microarray expression profiling as a discovery tool to identify the signaling networks involved. Resistance acquisition led to dysregulation of genes associated with irinotecan resistance, including TOP1, drug-metabolizing enzymes (CYPs and UGTs), and efflux transporters (ABCs), while also affecting the extression of 53 genes involed in proliferation and 33 in cell motility. Curcumin treatment significantly modulated 3,901 genes (FC >|±2|), inducing apoptosis, reducing proliferation, and inhibiting migration. Curcumin also enhanced sensitivity to irinotecan, by upregulating TOP1 and inhibiting 18 CYPs, 4 UGTs, and 20 ABCs, including those upregulated in irinotecan-resistant cells. An irinotecan-resistant CRC cell line (DLD1_IRI-R) was established by exposing DLD1 cells to increasing irinotecan concentrations, until cells would survive and proliferate in culture medium containing 20 μM irinotecan. The whole transcriptome analysis was implemented in four biological replicas of DLD1_IRI-R cells and the resistant cells treated for 48h with curcumin at IC50 concentration.