The Multidrug Resistance‐associated Protein Gene Confers Drug Resistance in Human Gastric and Colon Cancers

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Abstract
To determine the expression of multidrug resistance‐associated protein (MRP) gene and its role in gastric and colon cancers, we analyzed 10 gastric and 10 colon non‐drug‐selected cell lines and a similar number of tissue samples of these cancers. We compared the expression of MRP and mdr1 mRNA in cell lines and tissues using reverse‐transcriptase polymerase chain reaction. In mdr1‐negative cells, the relationship between the level of MRP gene expression and sensitivity to anticancer drugs was examined. The effect of verapamil, an MRP‐modulating agent, was also examined in these cells. The expression of MRP gene in gastric cancer cell lines varied from a low to a high level, but mdr1 was not detected in any of these cell lines. Colon cancer cell lines expressed low to intermediate levels of MRP gene, and half of the cells co‐expressed low to high levels of mdr1. In tissue samples, the expression pattern of the two multidrug resistance (MDR) genes was broadly similar to that described for the cell lines, except that most of the gastric cancer tissue samples did express low levels of mdr1. No significant correlation was observed between the level of MRP gene expression and sensitivity to anticancer drugs in gastric and colon cell lines. However, verapamil significantly increased the sensitivity to etoposide, doxorubicin and vincristine in cells highly expressing MRP gene. Our results indicate that MRP gene may be important in conferring MDR in gastric and colon cancer cells.