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

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, KF28(TX) and KFr13(TX), 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, KF28(TX) and KFr13(TX) 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 AX-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 KF28(TX) and KFr13(TX) 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.