Expression of glutathione s-transferasepi and sensitivity of human gastric cancer cells to cisplatin

Abstract

Background. The authors examined the correlation between the expression of glutathione S‐transferase‐pi (GSTπ) and the sensitivity of gastric cancer to anticancer agents. Methods. In 62 human gastric carcinomas, the expression of GSTπ was immunohistochemically evaluated, and sensitivity to the anticancer drugs, cisplatin (CDDP), doxorubicin (DXR) aclacinomycin A (aclarubicin), (ACR), 5‐fluorouracil (5‐FU), mitomycin C (MMC) and carboquone (carbazilquinon) (CQ) was examined using the in vitro succinate dehydrogenase inhibition test. The authors used the Chinese hamster ovary (CHO) cell line and its variant CDDP‐resistant cell line C/CDP‐2, and they analyzed the relationship among CDDP‐sensitivity, mRNA expression, and immunohistochemical staining. Results. Immunohistochemically detected GST‐π‐positive tumors were noted in 35 of 62 excised tumors. There was no significant correlation between GST‐π‐expression and clinicopathologic features or prognosis. The succinate dehydrogenase activity of each drug for tumors, with regard to negative or positive GST‐π, was 34.9 plus or minus 13.7% and 46.0 plus or minus 22.0% for CDDP, with a significant statistical difference (P < 0.05). However, there was no statistical difference for the other drugs tested. C/CDP‐2 cells showed a lower sensitivity to CDDP, a higher expression of mRNA for GSTπ and a stronger immunohistochemical staining than CHO cells. Conclusions. The overexpression of GST‐π is significantly related to the sensitivity of gastric cancer to CDDP.

Human hepatoma cells rich in P-glycoprotein are sensitive to aclarubicin and resistant to three other anthracyclines

“…Our findings strongly indicate that ACL is a poor substrate for active outward transport by Pgp, which is in agreement with previous reports of MDR circumvention with 9-alkyl or morpholinyl substituted anthracyclines in cell lines (Scott et al, 1986;Streeter et al, 1986;Coley et al, 1990). Two recent reports suggest that ACL may also circumvent drug resistance due to altered expression of topoisomerase II and glutathione S-transferase (Jensen et al, 1993;Okuyama et al, 1994). The assessment of cytotoxicity was performed using growth inhibition assays that measure cell growth by electronic cell counting.…”

Proteomic analysis of hematopoietic stem cell-like fractions in leukemic disorders

“…GST functions in cellular detoxification by catalysing the conjugation of reduced glutathione (GSH) to target molecules. In addition, GST-pi has been linked to chemoresistance to doxorubicin (Volm et al, 1992) and to cisplatin (Okuyama et al, 1994), and GST isoforms have been shown to be directly regulated by c-Jun NH 2 -terminal kinase (JNK), also known as stress-activated protein kinase (SAPK) (Adler et al, 1999). SOD2, also known as manganese-dependent SOD (MnSOD), is a mitochondrial enzyme that catalyses dismutation of the superoxide anion into O 2 and H 2 O 2 .…”

Glutathione-S-transferase activity and isoenzyme levels measured by two methods in ovarian cancer, and their value as markers of disease outcome

“…In node-negative breast cancer increased GST acidic isoenzyme measured immunohistochemically was associated with decreased disease-free survival and overall survival (Gilbert et al, 1993), but there was no correlation between the level of GST isoenzyme expression and the length of disease-free survival in nodepositive breast cancer when the isoenzymes were quantified by Western blot (Peters et al, 1993). In gastric cancer an immunohistochemical study showed no significant correlation between GST acidic isoenzyme expression and clinicopathological features or prognosis (Okuyama et al, 1994), but in oral cancer the acidic isoenzyme was considered to be a useful aid to early diagnosis, prediction of disease extent and outcome (Hirata et al, 1992). Immunohistochemical measurements of neutral isoenzymes have shown a positive correlation with survival in childhood acute lymphoblastic leukaemia (Hall et al, 1994), and of acidic isoenzymes with survival in non-lymphoblastic leukaemia in adults (Koberda and Hellman, 1994).…”