Oguchi H, Kikkawa F, Kojima M, Maeda O, Mizuno K, Suganuma N, Kawai M, Tomoda Y
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Anticancer Res. 1994 Jan-Feb;14(1A):193-200.
A cis-diamminedichloroplatinum (II) (CDDP)-resistant cell line (NOS2CR) demonstrated 7.4-fold greater resistance to CDDP compared with the parental cell line (NOS2) established from a patient with serous cystadenocarcinoma of the ovary. We investigated the role of enzyme systems associated with glutathione (GSH) in these cell lines. The GSH content was almost identical in both cell lines. Preincubation with 50 microM DL-buthionine-S, R-sulfoximine (BSO), an inhibitor of gamma-glutamyl cysteine synthetase, for 24 hr reduced the IC50 in both NOS2 and NOS2CR cells. Glutathione-S-transferase pi (GST-pi) activity and mRNA level in NOS2CR cells were higher than in NOS2 cells. However, gamma-glutamyltranspeptidase (GGT) activity in NOS2CR cells was 2.4-fold less than in NOS2 cells. The GST activity and mRNA level in both cell lines were constant when the cells were exposed to CDDP. Exposure to CDDP for 48 hr increased the GGT mRNA level 4.4 and 1.8 times in NOS2 and NOS2CR cells, respectively, compared with no exposure. By exposure to CDDP for 48 hr, the GGT activities in NOS2 and NOS2CR cells were increased 1.6-and 2.5-fold, respectively, compared with no exposure. The above data provide the first evidence that GGT activity and GGT mRNA are induced by CDDP in human carcinoma cell lines.
一种顺二氯二氨铂（II）（CDDP）耐药细胞系（NOS2CR）对CDDP的耐药性比从一名卵巢浆液性囊腺癌患者建立的亲本细胞系（NOS2）高7.4倍。我们研究了与谷胱甘肽（GSH）相关的酶系统在这些细胞系中的作用。两种细胞系中的GSH含量几乎相同。用50微摩尔的γ-谷氨酰半胱氨酸合成酶抑制剂DL-丁硫氨酸-S，R-亚砜亚胺（BSO）预孵育24小时可降低NOS2和NOS2CR细胞中的IC50。NOS2CR细胞中的谷胱甘肽-S-转移酶pi（GST-pi）活性和mRNA水平高于NOS2细胞。然而，NOS2CR细胞中的γ-谷氨酰转肽酶（GGT）活性比NOS2细胞低2.4倍。当细胞暴露于CDDP时，两种细胞系中的GST活性和mRNA水平保持不变。与未暴露相比，暴露于CDDP 48小时后，NOS2和NOS2CR细胞中的GGT mRNA水平分别增加了4.4倍和1.8倍。与未暴露相比，暴露于CDDP 48小时后，NOS2和NOS2CR细胞中的GGT活性分别增加了1.6倍和2.5倍。上述数据首次证明了在人癌细胞系中CDDP可诱导GGT活性和GGT mRNA。
