Expression of glutathione S-transferase-pi and sensitivity of human gastric cancer cells to cisplatin

Cancer. 1994 Aug 15;74(4):1230-6. doi: 10.1002/1097-0142(19940815)74:4<1230::aid-cncr2820740409>3.0.co;2-0.

Abstract

Background: The authors examined the correlation between the expression of glutathione S-transferase-pi (GST pi) and the sensitivity of gastric cancer to anticancer agents.

Methods: In 62 human gastric carcinomas, the expression of GST pi 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-pi-positive tumors were noted in 35 of 62 excised tumors. There was no significant correlation between GST-pi expression and clinicopathologic features or prognosis. The succinate dehydrogenase activity of each drug for tumors, with regard to negative or positive GST-pi, 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 GST pi and a stronger immunohistochemical staining than CHO cells.

Conclusions: The overexpression of GST-pi is significantly related to the sensitivity of gastric cancer to CDDP.

MeSH terms

  • Aclarubicin / pharmacology
  • Animals
  • CHO Cells
  • Carbazilquinone / pharmacology
  • Carcinoma / enzymology*
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Carcinoma / physiopathology
  • Cell Nucleus / enzymology
  • Cell Nucleus / ultrastructure
  • Cisplatin / pharmacology*
  • Cricetinae
  • Cytoplasm / enzymology
  • Cytoplasm / ultrastructure
  • Doxorubicin / pharmacology
  • Drug Resistance
  • Female
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Glutathione Transferase / analysis
  • Glutathione Transferase / genetics*
  • Humans
  • Isoenzymes / analysis
  • Isoenzymes / genetics*
  • Male
  • Middle Aged
  • Mitomycin / pharmacology
  • Prognosis
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / physiopathology
  • Succinate Dehydrogenase / antagonists & inhibitors
  • Survival Rate

Substances

  • Isoenzymes
  • RNA, Messenger
  • Carbazilquinone
  • Mitomycin
  • Aclarubicin
  • Doxorubicin
  • Succinate Dehydrogenase
  • Glutathione Transferase
  • Cisplatin
  • Fluorouracil