title: Characterization of two independent, exposure-time dependent paclitaxel-resistant human ovarian carcinoma cell lines.
abstract: This experiment was conducted to address the question of whether acquired paclitaxel resistance is dependent upon whether it is given as a single brief exposure or as a long-term exposure. PX2 and PX24 were established from 2008 human ovarian cancer cells by 2-h single exposure or 24-h continuous exposure to paclitaxel. PX2 acquired paclitaxel resistance faster than PX24 by twofold. Drug resistant pattern was exposure-time dependent. In 2-h exposure, PX2 showed 53.86 ± 4.96 (mean ± standard deviation [SD]) fold paclitaxel resistance while PX24 showed 9.51 ± 1.01 fold resistance (P = 0.002). In 24-h exposure, PX2 showed 2.31 ± 0.3 fold paclitaxel resistance while PX24 showed 28.17 ± 0.98 fold resistance (P = 0.040). PX2 and PX24 acquired cross-resistance to docetaxel and SN38 and the resistance degrees were significantly higher in PX2 than PX24. They displayed approximately twofold cisplatin collateral sensitivity. PX24 also displayed sensitivity to other platinum drugs, oxaliplatin and ZD0473, whereas PX2 acquired significant resistance to both of them. Although differential tubulin-isotype expressions were noted among 2008, PX2 and PX24, they were not significant. In electron microscopy, prominent, densely stained lysosomes were observed more in the resistant cells than 2008. Two independent, exposure-time dependent paclitaxel-resistant human ovarian carcinoma cell lines were established. Understanding the characteristics of the differential resistance pattern could be clinically beneficial for the selection of second line chemotherapy for relapsed ovarian cancer.
authors.affiliation: Department of Obstetrics/Gynecology Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kuninobu
authors.initials: K
authors.lastname: Nakajima
authors.forename: Seiji
authors.initials: S
authors.lastname: Isonishi
authors.forename: Misato
authors.initials: M
authors.lastname: Saito
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tachibana
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikawa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000196:embryology / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008854:Microscopy, Electron; D008870:Microtubules; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology*; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D050257:Tubulin Modulators; D017239:Paclitaxel