Kikuchi Y, Iwano I, Miyauchi M, Kita T, Oomori K, Kizawa I, Sugita M, Tenjin Y
Department of Obstetrics and Gynecology, National Defense Medical College, Saitama.
Jpn J Cancer Res. 1988 May;79(5):632-5. doi: 10.1111/j.1349-7006.1988.tb00033.x.
The present study was designed to elucidate the mechanism of resistance to cisplatin. A cisplatin-resistant cell line (KFr) was established from KF cells derived from human serous cystadenocarcinoma of the ovary. The DNA histogram revealed an increase of S-phase cells and a decrease of G1-phase cells in cultured KFr cells, compared to that in cultured KF cells. Although the cisplatin content in the KF cells incubated with cisplatin at 10 micrograms/ml increased in a time-dependent manner, that in the KFr cells remained unchanged during the experimental period. When 0.5 mg of cisplatin was administered ip to nude mice with KF or KFr tumor, the cisplatin content in the KFr tumor was significantly lower than that in the KF tumor. The KFr cells showed a cross-resistance to L-phenylalanine mustard, while no cross-resistance to vincristine or 5-fluorouracil was observed. These findings suggest that the mechanism of cisplatin resistance in the KFr cells involves a decrease of cisplatin accumulation in the tumor cells.
本研究旨在阐明对顺铂耐药的机制。从人卵巢浆液性囊腺癌来源的KF细胞建立了顺铂耐药细胞系(KFr)。与培养的KF细胞相比,DNA直方图显示培养的KFr细胞中S期细胞增加,G1期细胞减少。尽管用10微克/毫升顺铂孵育的KF细胞中顺铂含量呈时间依赖性增加,但在实验期间KFr细胞中的顺铂含量保持不变。当向携带KF或KFr肿瘤的裸鼠腹腔注射0.5毫克顺铂时,KFr肿瘤中的顺铂含量明显低于KF肿瘤。KFr细胞对L-苯丙氨酸氮芥表现出交叉耐药性,而未观察到对长春新碱或5-氟尿嘧啶的交叉耐药性。这些发现表明,KFr细胞中顺铂耐药的机制涉及肿瘤细胞中顺铂积累的减少。