In-vitro schedule-dependent interaction between oxaliplatin and 5-fluorouracil in human gastric cancer cell lines

Baoli Qin, Risa Tanaka, Yoshihiro Shibata, Shuji Arita, hiroshi ariyama, Hitoshi Kusaba, Eishi Baba, Mine Harada, Shuji Nakano

研究成果: ジャーナルへの寄稿記事

9 引用 (Scopus)

抄録

In order to define the most effective combination schedule of oxaliplatin (L-OHP) and 5-fluorouracil (5-FU), we investigated the in vitro interaction between these drugs in a panel of four human gastric adenocarcinoma cell lines (MKN-1, NUGC-3, NUGC-5 and AZ-521). Cytotoxic activity was determined by the WST-1 assay. Different 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. Simultaneous and sequential treatments of L-OHP followed by 5-FU exhibited synergistic effects in all four cell lines, whereas the reverse sequence yielded a clear antagonism. 5-FU exclusively arrested cells at the G0/G1 phase, and L-OHP at the G0/G1 and G2/M phases. Apoptosis was most prominent when cells were treated simultaneously or in a sequence of L-OHP followed by 5-FU, producing apoptosis in the majority of treated cells (55.5-61.5%). In contrast, the reverse sequence yielded only 20% induction of apoptosis, the rate being not significantly different from those induced by each drug singly. Moreover, this sequence dependence was further confirmed by the experiment which compared the total number of NUGC-3 cells 7 days after these combination schedules. These findings suggest that the interaction of 5-FU and L-OHP could be highly schedule dependent, with the most efficacious interaction observed in simultaneous combination and that 5-FU followed by L-OHP would not be recommended in clinical trials for patients with advanced gastric cancer.

元の言語英語
ページ(範囲)445-453
ページ数9
ジャーナルAnti-Cancer Drugs
17
発行部数4
DOI
出版物ステータス出版済み - 4 1 2006

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oxaliplatin
Fluorouracil
Stomach Neoplasms
Appointments and Schedules
Cell Line
Apoptosis
Cell Cycle Resting Phase
G2 Phase
G1 Phase
Drug Interactions
Pharmaceutical Preparations
Cell Division
In Vitro Techniques
Stomach
Cell Cycle
Flow Cytometry
Adenocarcinoma

All Science Journal Classification (ASJC) codes

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

これを引用

In-vitro schedule-dependent interaction between oxaliplatin and 5-fluorouracil in human gastric cancer cell lines. / Qin, Baoli; Tanaka, Risa; Shibata, Yoshihiro; Arita, Shuji; ariyama, hiroshi; Kusaba, Hitoshi; Baba, Eishi; Harada, Mine; Nakano, Shuji.

:: Anti-Cancer Drugs, 巻 17, 番号 4, 01.04.2006, p. 445-453.

研究成果: ジャーナルへの寄稿記事

Qin, Baoli ; Tanaka, Risa ; Shibata, Yoshihiro ; Arita, Shuji ; ariyama, hiroshi ; Kusaba, Hitoshi ; Baba, Eishi ; Harada, Mine ; Nakano, Shuji. / In-vitro schedule-dependent interaction between oxaliplatin and 5-fluorouracil in human gastric cancer cell lines. :: Anti-Cancer Drugs. 2006 ; 巻 17, 番号 4. pp. 445-453.
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abstract = "In order to define the most effective combination schedule of oxaliplatin (L-OHP) and 5-fluorouracil (5-FU), we investigated the in vitro interaction between these drugs in a panel of four human gastric adenocarcinoma cell lines (MKN-1, NUGC-3, NUGC-5 and AZ-521). Cytotoxic activity was determined by the WST-1 assay. Different 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. Simultaneous and sequential treatments of L-OHP followed by 5-FU exhibited synergistic effects in all four cell lines, whereas the reverse sequence yielded a clear antagonism. 5-FU exclusively arrested cells at the G0/G1 phase, and L-OHP at the G0/G1 and G2/M phases. Apoptosis was most prominent when cells were treated simultaneously or in a sequence of L-OHP followed by 5-FU, producing apoptosis in the majority of treated cells (55.5-61.5{\%}). In contrast, the reverse sequence yielded only 20{\%} induction of apoptosis, the rate being not significantly different from those induced by each drug singly. Moreover, this sequence dependence was further confirmed by the experiment which compared the total number of NUGC-3 cells 7 days after these combination schedules. These findings suggest that the interaction of 5-FU and L-OHP could be highly schedule dependent, with the most efficacious interaction observed in simultaneous combination and that 5-FU followed by L-OHP would not be recommended in clinical trials for patients with advanced gastric cancer.",
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AU - Tanaka, Risa

AU - Shibata, Yoshihiro

AU - Arita, Shuji

AU - ariyama, hiroshi

AU - Kusaba, Hitoshi

AU - Baba, Eishi

AU - Harada, Mine

AU - Nakano, Shuji

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N2 - In order to define the most effective combination schedule of oxaliplatin (L-OHP) and 5-fluorouracil (5-FU), we investigated the in vitro interaction between these drugs in a panel of four human gastric adenocarcinoma cell lines (MKN-1, NUGC-3, NUGC-5 and AZ-521). Cytotoxic activity was determined by the WST-1 assay. Different 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. Simultaneous and sequential treatments of L-OHP followed by 5-FU exhibited synergistic effects in all four cell lines, whereas the reverse sequence yielded a clear antagonism. 5-FU exclusively arrested cells at the G0/G1 phase, and L-OHP at the G0/G1 and G2/M phases. Apoptosis was most prominent when cells were treated simultaneously or in a sequence of L-OHP followed by 5-FU, producing apoptosis in the majority of treated cells (55.5-61.5%). In contrast, the reverse sequence yielded only 20% induction of apoptosis, the rate being not significantly different from those induced by each drug singly. Moreover, this sequence dependence was further confirmed by the experiment which compared the total number of NUGC-3 cells 7 days after these combination schedules. These findings suggest that the interaction of 5-FU and L-OHP could be highly schedule dependent, with the most efficacious interaction observed in simultaneous combination and that 5-FU followed by L-OHP would not be recommended in clinical trials for patients with advanced gastric cancer.

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