Evaluation of FDA Drugs to Identify Modulators of Multidrug Resistance Associated Protein 1 (MRP1) Expression Levels in HEK293 MRP1 Overexpressing Cells.

Abstract

The Multidrug Resistance Associated Protein 1 is a key feature in drug resistance within cancerous cells. This protein is involved in efflux of a broad spectrum of substrates, including organic anions and several chemical therapeutic agents, like doxorubicin. In addition, MRP1 has implications in separate physiologies such as cardiovascular disease and age‐related macular degradation. As such, its overexpression has been implicated in multidrug resistance of several cancers. This project is aimed at evaluating the effect of chemotherapeutic agents on the expression levels of MRP1 in HEK293/MRP1 cells. A unique library of FDA drugs were screened using a high throughput In‐Cell ELISA Assay. A total of 88 drugs were screened. Drugs that showed modulation of MRP1 protein expression above 30% were considered as Hit compounds. A significant number of hits were identified, from which some of the drugs increased MRP1 protein expression and decreased its expression. This protein enhances the cells ability to efflux toxic compounds, such as anticancer drugs, out of the cell. A cell’s ability to increase expression of this protein results from a genetic mutation. As a result, higher concentrations of traditional anticancer drug compounds are required to demonstrate similar results as cells that do not over express MRP1. However, discovery of drugs that can decrease the expression of this protein would play a valuable role in assisting the fight against cancer. Support or Funding Information I would like to thank Jack and Mary East for their support and funding for this project