Schedule-dependent synergistic interaction between gemcitabine and oxaliplatin in human gallbladder adenocarcinoma cell lines

Akitaka Makiyama, Baoli Qin, Keita Uchino, Yoshihiro Shibata, Shuji Arita, Taichi Isobe, Gen Hirano, Hitoshi Kusaba, Eishi Baba, Koichi Akashi, Shuji Nakano

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

To define the most effective combination schedule of gemcitabine and oxaliplatin (L-OHP), we investigated the in-vitro interaction between these drugs in a panel of four human gallbladder adenocarcinoma cell lines (HAG-1, GB- d1, NOZ, and G-415). 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 gemcitabine followed by L-OHP exhibited synergistic effects in all four cell lines, whereas the reverse sequence largely showed an antagonism. Gemcitabine exclusively arrested cells at the G o/G 1 phase, and L-OHP at the G 2/M phase, as measured by flow cytometric analyses. Apoptosis was most prominent when cells were treated simultaneously or in a sequence gemcitabine followed by L-OHP, producing apoptosis in treated cells (27-30%). In contrast, the reverse sequence yielded only 6-7% 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 number of HAG-1 cells 7 days after these combination schedules. These findings suggest that the interaction of gemcitabine and L-OHP is highly schedule dependent with the most efficacious interaction observed in either simultaneous combination or in a sequence combination of gemcitabine followed by L-OHP.

元の言語英語
ページ(範囲)123-130
ページ数8
ジャーナルAnti-cancer drugs
20
発行部数2
DOI
出版物ステータス出版済み - 2 1 2009

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oxaliplatin
gemcitabine
Gallbladder
Appointments and Schedules
Adenocarcinoma
Cell Line
Apoptosis
Gastrin-Secreting Cells
Drug Interactions
Pharmaceutical Preparations
Cell Division
Cell Cycle
Flow Cytometry

All Science Journal Classification (ASJC) codes

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

これを引用

Schedule-dependent synergistic interaction between gemcitabine and oxaliplatin in human gallbladder adenocarcinoma cell lines. / Makiyama, Akitaka; Qin, Baoli; Uchino, Keita; Shibata, Yoshihiro; Arita, Shuji; Isobe, Taichi; Hirano, Gen; Kusaba, Hitoshi; Baba, Eishi; Akashi, Koichi; Nakano, Shuji.

:: Anti-cancer drugs, 巻 20, 番号 2, 01.02.2009, p. 123-130.

研究成果: ジャーナルへの寄稿記事

Makiyama, Akitaka ; Qin, Baoli ; Uchino, Keita ; Shibata, Yoshihiro ; Arita, Shuji ; Isobe, Taichi ; Hirano, Gen ; Kusaba, Hitoshi ; Baba, Eishi ; Akashi, Koichi ; Nakano, Shuji. / Schedule-dependent synergistic interaction between gemcitabine and oxaliplatin in human gallbladder adenocarcinoma cell lines. :: Anti-cancer drugs. 2009 ; 巻 20, 番号 2. pp. 123-130.
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AU - Makiyama, Akitaka

AU - Qin, Baoli

AU - Uchino, Keita

AU - Shibata, Yoshihiro

AU - Arita, Shuji

AU - Isobe, Taichi

AU - Hirano, Gen

AU - Kusaba, Hitoshi

AU - Baba, Eishi

AU - Akashi, Koichi

AU - Nakano, Shuji

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