卵巢透明细胞癌中顺铂耐药的机制

Mechanisms of cisplatin resistance in clear cell carcinoma of the ovary.

作者信息

Itamochi Hiroaki, Kigawa Junzo, Akeshima Ryoji, Sato Shinya, Kamazawa Shunji, Takahashi Masakuni, Kanamori Yasunobu, Suzuki Mitsuaki, Ohwada Michitaka, Terakawa Naoki

机构信息

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

出版信息

Oncology. 2002;62(4):349-53. doi: 10.1159/000065067.

DOI:10.1159/000065067

PMID:12138243

Abstract

Resistance of clear cell carcinoma (CCC) of the ovary to platinum-based chemotherapy is associated with a poor prognosis. However, the mechanism underlying the resistance of CCC to platinum has not yet been understood. We conducted the present study to clarify the mechanism of cisplatin (CDDP) resistance in CCC cells. Eleven CCC and 5 serous adenocarcinoma (SAC) cell lines were used in this study. The IC(50) to CDDP ranged from 1.3 to 18.0 microM for CCC cells and from 2.2 to 13.0 microM for SAC cells. There was no correlation between multidrug resistance-associated protein expression and the sensitivity to CDDP in CCC cells. In contrast, the doubling time for CCC cells was significantly longer than that for SAC cells (61.4 vs. 29.8 h). A significant reverse correlation between the S-phase fraction and the response to CDDP was observed (r = 0.647, p < 0.05). The present study suggests that the resistance of CCC to CDDP may be caused by low cell proliferation.

摘要

卵巢透明细胞癌（CCC）对铂类化疗的耐药与预后不良相关。然而，CCC对铂耐药的潜在机制尚未明确。我们开展本研究以阐明CCC细胞对顺铂（CDDP）耐药的机制。本研究使用了11种CCC细胞系和5种浆液性腺癌（SAC）细胞系。CCC细胞对CDDP的半数抑制浓度（IC50）范围为1.3至18.0微摩尔，SAC细胞为2.2至13.0微摩尔。在CCC细胞中，多药耐药相关蛋白表达与对CDDP的敏感性之间无相关性。相反，CCC细胞的倍增时间显著长于SAC细胞（61.4小时对29.8小时）。观察到S期细胞比例与对CDDP反应之间存在显著的负相关（r = 0.647，p < 0.05）。本研究提示，CCC对CDDP的耐药可能是由细胞增殖缓慢所致。