谷胱甘肽S-转移酶π的表达与人胃癌细胞对顺铂的敏感性

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

作者信息

Okuyama T, Maehara Y, Endo K, Baba H, Adachi Y, Kuwano M, Sugimachi K

机构信息

Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

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

DOI:10.1002/1097-0142(19940815)74:4<1230::aid-cncr2820740409>3.0.co;2-0

PMID:8055443

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.

摘要

背景

作者研究了谷胱甘肽S-转移酶π（GST π）的表达与胃癌对抗癌药物敏感性之间的相关性。

方法

对62例人类胃癌进行免疫组织化学评估，检测GST π的表达，并使用体外琥珀酸脱氢酶抑制试验检测对顺铂（CDDP）、阿霉素（DXR）、阿克拉霉素A（阿克拉比星）（ACR）、5-氟尿嘧啶（5-FU）、丝裂霉素C（MMC）和卡波醌（卡巴醌）（CQ）等抗癌药物的敏感性。作者使用中国仓鼠卵巢（CHO）细胞系及其顺铂耐药变异细胞系C/CDP-2，分析顺铂敏感性、mRNA表达和免疫组织化学染色之间的关系。

结果

在62例切除的肿瘤中，有35例免疫组织化学检测到GST-π阳性肿瘤。GST-π表达与临床病理特征或预后之间无显著相关性。对于GST-π阴性或阳性的肿瘤，每种药物的琥珀酸脱氢酶活性，顺铂分别为34.9±13.7%和46.0±22.0%，有显著统计学差异（P<0.05）。然而，对于其他测试药物，没有统计学差异。C/CDP-2细胞对顺铂的敏感性较低，GST π的mRNA表达较高，免疫组织化学染色比CHO细胞更强。