Lapatinib induced-changes in Caco-2 intestinal monolayer via ErbB1 inhibition / Raja Nur Firzanah Syaza Raja Sharin

Lapatinib (LAP) is an orally administered dual ErbBl and ErbB2 tyrosine kinase inhibitor for ErbB2-positive breast tumours, but is associated with diarrhoea. Incidence of lapatinib-induced diarrhoea (LID) is as high as 58-78% in treated patients. Although short-term diarrhoea is tolerable, prolonged diarrhoea can cause hospitalisation and interfere with cancer treatment, thus compromising the quality of life of patients with cancer. ErbBl is widely expressed in the intestine which functions to maintain homeostasis. Therefore, it is hypothesised that LAP inhibits ErbBl normal physiological in the intestine, leading to diarrhoea. This study aimed to investigate possible changes in Caco-2 intestinal monolayer following LAP treatment due to ErbB 1 inhibition. Several parameters such as intestinal permeability changes, alteration of tight junctions and intestinal inflammation due to ErbBl inhibition were studied using Caco-2 cells. Caco-2 is a colon cancer cell line, but it can differentiate into enterocytes and mimic normal intestinal cultures. Prior to Caco-2 differentiation, cytotoxic effect of LAP and LAP+recombinant epidermal growth factor (LAP+rEGF) on Caco-2 were evaluated at 24, 48, 72 and 96 hours using WST-1 assay. Caco-2 cells were seeded in a transwell insert for 21 days to form an intestinal epithelial monolayer prior to treatment. Monolayer integrity and permeability were assessed via transepithelial electrical resistance (TEER) and Lucifer yellow (LY) assay.