GlutathioneS-transferase-? expression and glutathione concentration in ovarian carcinoma before and after chemotherapy

Abstract

To clarify the role of glutathione (GSH) in the chemotherapy resistance of ovarian carcinoma, the authors examined the expression of glutathione S-transferase-pi (GST-pi) and the concentration of glutathione in tumors before and after chemotherapy in the same patients. The cohort for this study comprised 20 patients with ovarian carcinoma who had residual disease after primary surgery. These patients received two to three courses of postoperative chemotherapy, then underwent surgery for a second time. Chemotherapy consisted of 50 mg/m2 cisplatin, 40 mg/m2 doxorubicin, and 400 mg/m2 cyclophosphamide. The expression of GST-pi in tumors was determined by immunohistochemical staining and Western blot analysis. GSH concentration was measured by an enzymatic assay. Of the 20 patients, 10 responded to chemotherapy and 10 did not. Immunohistochemical staining for GST-pi was positive in 3 tumors among the 10 responders and in 7 tumors among the 10 nonresponders, but Western blot analysis detected GST-pi expression in all tumors. Among the responders, GST-pi after chemotherapy increased in one patient, was unchanged in two patients, and decreased in seven patients. Among nonresponders, GST-pi increased in six patients, was unchanged in one patient, and decreased in three patients. The ratio of GST-pi density in tumors after chemotherapy to GST-pi density before chemotherapy was significantly higher in nonresponders than in responders (2.0 +/- 1.1 vs. 0.6 +/- 0.4). The concentration of GSH in tumors was widely distributed, but it was found that the ratio of GSH concentration in each tumor after chemotherapy to GSH concentration before chemotherapy was significantly higher for nonresponders than for responders (3.0 +/- 1.3 vs. 0.6 +/- 0.3). Increased levels of GST-pi expression after chemotherapy are linked to drug resistance in patients with ovarian carcinoma.