In vitro schedule-dependent interaction between paclitaxel and oxaliplatin in human cancer cell lines

Risa Tanaka, Hiroshi Ariyama, Baoli Qin, Yasushi Takii, Eishi Baba, Kenji Mitsugi, Mine Harada, Shuji Nakano

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose: In order to define the most effective administration schedule of the combination of paclitaxel and oxaliplatin, we investigated the in vitro interaction between these drugs in a panel of three human cancer cell lines (AZ-521 gastric adenocarcinoma cell line, HST-1 tongue squamous carcinoma cell line, and KSE-1 esophageal squamous carcinoma cell line). Materials and methods: Cytotoxic activity was determined by the WST-1 assay. Different administration schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism with a quantitative method based on the median-effect principle of Chou and Talalay. Cell cycle perturbation and apoptosis were evaluated by flow cytometry. Results: Simultaneous treatment of cells with paclitaxel and oxaliplatin showed greater than additive effects. Upon 24-h sequential exposure, the sequence of paclitaxel followed by oxaliplatin showed synergistic effects in AZ-521 and HST-1 cells, and greater than additive effects in KSE-1 cells, while the opposite sequence yielded marked antagonistic effects in all three cell lines. Flow cytometric analysis indicated that paclitaxel induced G2/M arrest with subsequent induction of apoptosis in the sub-G1 phase. Apoptosis was most prominent when paclitaxel preceded oxaliplatin, which produced apoptosis in the majority of treated cells (75%). By contrast, the reverse sequence yielded only 39% induction of apoptotic cells, the rate being not different from those induced by each drug singly. Conclusions: Our findings suggest that the interaction of paclitaxel and oxaliplatin is highly schedule-dependent and that the sequential administration of paclitaxel followed by oxaliplatin should thus be incorporated into the design of a clinical trial.

Original languageEnglish
Pages (from-to)595-601
Number of pages7
JournalCancer chemotherapy and pharmacology
Volume55
Issue number6
DOIs
Publication statusPublished - Jun 1 2005

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this