Glutathione, glutathione S-transferase α and π and aldehyde dehydrogenase content in relationship to drug resistance in ovarian cancer

• Published in: Gynecologic oncology Vol. 65; no. 1; pp. 54 - 62
• Main Authors: TANNER, B, HENGSTLER, J. G, DIETRICH, B, HENRICH, M, STEINBERG, P, WEIKEL, W, MEINERT, R, KAINA, B, OESCH, F, KNAPSTEIN, P. G
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 01.04.1997
• Subjects: Aldehyde Dehydrogenase - analysis; Antineoplastic Agents - therapeutic use; Antineoplastic Agents, Alkylating - therapeutic use; Biological and medical sciences; Blotting, Western; Carboplatin - therapeutic use; Cisplatin - therapeutic use; Combined Modality Therapy; Cyclophosphamide - therapeutic use; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Therapy, Combination; Female; Female genital diseases; Glutathione - analysis; Glutathione Transferase - analysis; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Neoplasm Staging; Ovarian Neoplasms - chemistry; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Prognosis; Tumors; Relapse; Ovary; Enzymatic activity; Etiology; Glutathione transferase; Female; Negative therapeutic reaction; Quantitative analysis; Glutathione; Human; Drug combination; Enzyme; Transferases; ); Malignant tumor; Female genital diseases; Ovarian diseases; Chemotherapy; Cyclophosphamide; Oxazaphosphinane derivatives; Treatment; Aldehyde dehydrogenase (NAD; Nitrogen mustard; Carboplatin; Oxidoreductases
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1006/gyno.1996.4593

Glutathione, glutathione S-transferases alpha and pi, and aldehyde dehydrogenase are associated with resistance to carboplatin and/or cyclophosphamide in cell lines. Therefore, we examined whether the expression of these factors in ovarian cancer tissue specimens is associated with resistance of the patients to combination chemotherapy with cyclophosphamide/carboplatin. Ovarian cancer tissue specimens were taken intraoperatively from 139 patients and frozen in liquid nitrogen, and the contents of glutathione S-transferases alpha and pi, total glutathione, and aldehyde dehydrogenase activity were determined. No association between the levels of glutathione S-transferases alpha and pi or aldehyde dehydrogenase activity in tumor tissue and the survival time was observed in patients with primary ovarian cancer. Significantly higher levels of aldehyde dehydrogenase were observed in FIGO stage I and II compared to FIGO stage III and IV tumors (P = 0.019, Wilcoxon test, two sided). The median survival time was significantly longer in patients with primary ovarian cancer with a tumor glutathione content of <4.9 microg/mg protein compared to patients with a tumor glutathione content of > or =4.9 microg/mg protein (P = 0.047). However, glutathione was not an independent prognostic factor, but was significantly associated with FIGO stage resulting in higher levels in FIGO stage III and IV tumors than in FIGO stage I and II tumors (P = 0.0094, Wilcoxon test, two sided). In conclusion the glutathione content was associated with progression of ovarian carcinomas but neither glutathione nor glutathione S-transferases alpha and pi or aldehyde dehydrogenase were independent factors of resistance to cyclophosphamide/carboplatin.