Modulation of cisplatin sensitivity by taxol in cisplatin-sensitive and -resistant human ovarian carcinoma cell lines.
OBJECTIVE
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.
Yamamoto
K
K
Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama, Japan. QWL04765@niftyserve.ne.jp
Kikuchi
Y
Y
Kudoh
K
K
Nagata
I
I
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D019450:Genes, MDR / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D002945:Cisplatin