紫杉醇对顺铂敏感和耐药的人卵巢癌细胞系顺铂敏感性的调节作用

Modulation of cisplatin sensitivity by taxol in cisplatin-sensitive and -resistant human ovarian carcinoma cell lines.

作者信息

Yamamoto K, Kikuchi Y, Kudoh K, Nagata I

机构信息

Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama, Japan.

出版信息

J Cancer Res Clin Oncol. 2000 Mar;126(3):168-72. doi: 10.1007/s004320050027.

DOI:10.1007/s004320050027

PMID:10741911

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12165178/

Abstract

PURPOSE

The aim of this study was to determine whether taxol can circumvent cisplatin resistance, using a KF28 cell line derived from human ovarian carcinoma and a cisplatin-resistant line, KFr13, derived from the parental cell line, KF28, and taxol-resistant cell lines, KF28TX and KFr13TX, derived from the respective parental counterpart.

METHODS

KF28 is a single-cell clone of the human ovarian carcinoma cell line KF. The cisplatin-resistant KFr13 subline was established by repeated exposure of the parent KF28 cell line to escalating doses of cisplatin. Similarly, KF28TX and KFr13TX were established by repeated exposure of the KF28 and KFr13 cell lines to escalating doses of taxol. A cytotoxicity assay was performed using a crystal violet staining method. Platinum and taxol accumulation were assayed by atomic absorption and reverse-phase high-performance liquid chromatography. The quantitative assay of MDR1 mRNA used polymerase chain reaction.

RESULTS

KFr13 cells were about 4.8-fold more resistant to cisplatin and about 1.8-fold more sensitive to taxol than were KF28 cells. When taxol resistance was induced in KF28 and KFr13 cells, sensitivity to cisplatin rose about 1.3- and 1.6-fold respectively. Elevation of sensitivity was correlated with platinum uptake by both KF28TX and KFr13TX cells. Expression of multidrug resistance (MDR1) mRNA, which was not observed in KF28 and KFr13 cells, was observed after induction of taxol resistance.

CONCLUSIONS

These results may suggest rational therapeutic strategies for patients with cisplatin-resistant or refractory ovarian carcinoma.

摘要

目的

本研究旨在利用源自人卵巢癌的KF28细胞系、源自亲代细胞系KF28的顺铂耐药细胞系KFr13以及源自各自亲代对应细胞系的紫杉醇耐药细胞系KF28TX和KFr13TX，确定紫杉醇是否能克服顺铂耐药性。

方法

KF28是人卵巢癌细胞系KF的单细胞克隆。顺铂耐药的KFr13亚系是通过将亲代KF28细胞系反复暴露于递增剂量的顺铂而建立的。同样，KF28TX和KFr13TX是通过将KF28和KFr13细胞系反复暴露于递增剂量的紫杉醇而建立的。使用结晶紫染色法进行细胞毒性测定。通过原子吸收和反相高效液相色谱法测定铂和紫杉醇的积累。MDR1 mRNA的定量测定使用聚合酶链反应。

结果

KFr13细胞对顺铂的耐药性比KF28细胞高约4.8倍，对紫杉醇的敏感性比KF28细胞高约1.8倍。当在KF28和KFr13细胞中诱导产生紫杉醇耐药性时，对顺铂的敏感性分别提高了约1.3倍和1.6倍。敏感性的提高与KF28TX和KFr13TX细胞对铂的摄取有关。在诱导产生紫杉醇耐药性后，观察到了多药耐药（MDR1）mRNA的表达，而在KF28和KFr13细胞中未观察到。