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

研究成果: ジャーナルへの寄稿記事

16 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)595-601
ページ数7
ジャーナルCancer Chemotherapy and Pharmacology
55
発行部数6
DOI
出版物ステータス出版済み - 6 1 2005

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oxaliplatin
Paclitaxel
Appointments and Schedules
Cells
Cell Line
Neoplasms
Apoptosis
Squamous Cell Carcinoma
Drug Administration Schedule
Pharmaceutical Preparations
Flow cytometry
G1 Phase
In Vitro Techniques
Drug Interactions
Tongue

All Science Journal Classification (ASJC) codes

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

これを引用

In vitro schedule-dependent interaction between paclitaxel and oxaliplatin in human cancer cell lines. / Tanaka, Risa; ariyama, hiroshi; Qin, Baoli; Takii, Yasushi; Baba, Eishi; Mitsugi, Kenji; Harada, Mine; Nakano, Shuji.

:: Cancer Chemotherapy and Pharmacology, 巻 55, 番号 6, 01.06.2005, p. 595-601.

研究成果: ジャーナルへの寄稿記事

Tanaka, Risa ; ariyama, hiroshi ; Qin, Baoli ; Takii, Yasushi ; Baba, Eishi ; Mitsugi, Kenji ; Harada, Mine ; Nakano, Shuji. / In vitro schedule-dependent interaction between paclitaxel and oxaliplatin in human cancer cell lines. :: Cancer Chemotherapy and Pharmacology. 2005 ; 巻 55, 番号 6. pp. 595-601.
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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.",
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AU - Tanaka, Risa

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AU - Qin, Baoli

AU - Takii, Yasushi

AU - Baba, Eishi

AU - Mitsugi, Kenji

AU - Harada, Mine

AU - Nakano, Shuji

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N2 - 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.

AB - 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.

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