The association between chemosensitivity and Pgp, GST-π and Topo II expression in gastric cancer

BACKGROUND: To investigate the relationship between P-glycoprotein (Pgp), glutathione S-transferase π (GST-π) and topoisomerase II (Topo II) expression and human gastric cancer chemoresistance in vitro. METHODS: Primary single-cell suspensions were prepared from fresh specimens of primary gastric cancer and exposed to hydroxycamptothecin (HCPT), cisplatin (CDDP), 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin (MMC) for 48 h. Cell metabolic activity and rate of inhibition were evaluated using tetrazolium (MTT) assay. Pgp, GST-π and Topo II expression was determined in gastric carcinoma tissue samples using immunohistochemistry. RESULTS: Chemosensitivity of the gastric cancer cells varied; the rates of inhibition of cells exposed to HCPT, CDDP and 5-FU were significantly higher than that of cells exposed to ADM and MMC (p < 0.05). Gastric cancer cells with Pgp expression were resistant to ADM and HCPT (p = 0.008 and p = 0.011, respectively). Cells resistant to 5-FU, CDDP and MMC had significantly higher GST-π expression (p < 0.05). Topo II expression was significantly lower in cells resistant to HCPT, ADM and MMC (p < 0.05). Pgp and GST-π expression may contribute to primary resistance of gastric cancer cells to some chemotherapeutic drugs, while Topo II expression may indicate HCPT, ADM and MMC sensitivity. CONCLUSIONS: Pgp, GST-π and Topo II detection and the MTT assay could be used as predictors in chemotherapeutic drug administration and for identifying drug resistance in gastric carcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3448329111142964.