Retention of paclitaxel in cancer cells for 1 week in vivo and in vitro

Cancer Chemotherapy and Pharmacology
Taisuke MoriHideo Honjo

Abstract

Clinically, the administration of paclitaxel for ovarian cancer on a dose-dense weekly schedule, rather than the conventional every-3-week schedule, might demonstrate greater tumor-cell death. Here, we investigate the pharmacokinetics and the pharmacodynamics of weekly paclitaxel in cancer cells in vivo and in vitro. Paclitaxel concentrations were measured by HPLC, and apoptotic cells were detected by TUNEL assay in paclitaxel-pretreated cervical cancer cells treated with paclitaxel (10 ng/ml) and in the tissues of cervical cancer patients treated with weekly paclitaxel (60 mg/m2/week). Polymerized tubulin was detected with a tubulin polymerization assay, and the BrdU cell proliferation assay was used to assess the effect of paclitaxel. Paclitaxel remained in the cancer tissues of six patients for 6 days after the last medication. In vitro, paclitaxel was retained in all cell lines for 24 h after its removal from the medium, and paclitaxel was still detectable in CaSki cells on day 7. Simultaneous treatment with depolymerizing drugs inhibited the retention of paclitaxel in cells and paclitaxel-induced polymerization of tubulin. After paclitaxel treatment, apoptotic cells were detected in cancer tissues and CaSki cells for 1 wee...Continue Reading

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