The effect of TRAIL on colorectal cancer

Abstract

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has been employed in many research experiments as a highly selective anti-tumour treatment against several cancer types, mostly colorectal cancers (CRCs). However, tumour cells tend to develop resistance to apoptosis through mutations that affect one or more proteins that are involves in the intrinsic or the extrinsic pathways of TRAIL; for example, mutations in B-cell CLL/ Lymphoma2 (Bcl-2) family of proteins. Here, TRAIL was tested on three CRC cell lines: HCT116, Caco-2, and DLD1 to identify the degree of sensitivity for each cell line. Due to the resistance observed in the three cell lines, TRAIL was combined with aspirin to increase their sensitivity to TRAIL-induced apoptosis. Aspirin is a non-steroidal anti-inflammatory drug that possesses antiproliferative properties. Although the mechanism in which aspirin works together with TRAIL is not fully understood yet, the results showed that aspirin significantly decreased the percentage cell viability even at as low a concentration as 2.5mM when used with 100ng/mL of TRAIL. Percentage cell viabilities were assessed using MTS assay. Moreover, when expression levels were analysed using Western blotting, using TRAIL and aspirin as a combination, increased the expression of the Heat Shock Protein 60 (HSP60) in the three cell lines, and increased the expression of Heat Shock Protein 27 (HSP27) in HCT116 and DLD-1 indicating the occurrence of high level of stress in cells due to the combined treatment when compared to the expression levels of the untreated cells and the cells which were treated with TRAIL alone.