Functional assessment of multidrug resistance in colorectal, pancreatic and liver malignancies

Introduction: ABC-MDR transporters have been suggested to play a role in resistance to chemotherapy in different malignant diseases.

Aim of the study: was to determine the functional MDR1 and MRP1 activity of colorectal, pancreatic and other gastrointestinal cancers with a novel functional method. (www.solvobiotech.com)

Methods: Endoscopic and surgical samples were taken from 51 colorectal, 13 pancreatic, and 13 metastatic liver carcinomas. Within six hours the samples were brought into one-cell solution via 10 minutes incubation with collagenase enzyme (Worthington Type IV, in 4mg/ml concentration). Washed with HBSS the cells were then treated with MRP1 and MDR1 blockers in the presence of Calcein-AM for another 10 minutes. The dead cells were stained with 7AAD (Dako) and the epithelial cells were detected by BerEP4 antibodies and Cy5-conjugated secondary antibodies in the presence of IgG1-isotype-control. The change in calcein-fluorescence intensity of the viable epithelial cells was evaluated with flow-cytometry.

Results: Increased ABC-MDR transporter function was found in 7/51 cases of colorectal cancers, 3/13 cases of pancreatic cancers and 1/13 case of metastatic liver diseases based on cut-off values previously demonstrated to correlate with clinical resistance to chemotherapy (Br J Haematol. 2001 Feb; 112 (2): 308–14).

Conclusion: A small proportion of patients undergoing surgery without prior chemotherapy had elevated MDR1 and MRP1 activity in the studied disease groups. Based on results on inflammatory bowel disease patients, MDR transporter-expression may be induced during chemotherapy. Assessment of transporter function during and subsequent to chemotherapy may be necessary for the objective evaluation of MDR function. Prospective trials are in progress.