化疗前后卵巢癌中谷胱甘肽S-转移酶π的表达及谷胱甘肽浓度

Glutathione S-transferase-pi expression and glutathione concentration in ovarian carcinoma before and after chemotherapy.

作者信息

Cheng X, Kigawa J, Minagawa Y, Kanamori Y, Itamochi H, Okada M, Terakawa N

机构信息

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.

出版信息

Cancer. 1997 Feb 1;79(3):521-7.

PMID:9028363

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

Increased levels of GST-pi expression after chemotherapy are linked to drug resistance in patients with ovarian carcinoma.

摘要

背景

为阐明谷胱甘肽（GSH）在卵巢癌化疗耐药中的作用，作者检测了同一批患者化疗前后肿瘤中谷胱甘肽S转移酶π（GST-π）的表达及谷胱甘肽的浓度。

方法

本研究队列包括20例初次手术后有残留病灶的卵巢癌患者。这些患者接受了两到三个疗程的术后化疗，然后再次接受手术。化疗方案为顺铂50mg/m²、阿霉素40mg/m²和环磷酰胺400mg/m²。通过免疫组织化学染色和蛋白质印迹分析确定肿瘤中GST-π的表达。采用酶法测定GSH浓度。

结果

20例患者中，10例对化疗有反应，10例无反应。免疫组织化学染色显示，10例有反应患者中的3个肿瘤及10例无反应患者中的7个肿瘤GST-π呈阳性，但蛋白质印迹分析在所有肿瘤中均检测到GST-π表达。有反应患者中，1例患者化疗后GST-π升高，2例不变，7例降低。无反应患者中，6例患者GST-π升高，1例不变，3例降低。无反应患者化疗后肿瘤中GST-π密度与化疗前GST-π密度之比显著高于有反应患者（2.0±1.1 vs. 0.6±0.4）。肿瘤中GSH浓度分布广泛，但发现无反应患者各肿瘤化疗后GSH浓度与化疗前GSH浓度之比显著高于有反应患者（3.0±1.3 vs. 0.6±0.3）。