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: Contribution to journalArticle査読

6 被引用数 (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.

本文言語英語
ページ(範囲)123-130
ページ数8
ジャーナルAnti-cancer drugs
20
2
DOI
出版ステータス出版済み - 2 1 2009

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 薬理学
  • 薬理学(医学)
  • 癌研究

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