Combining celecoxib with sorafenib synergistically inhibits hepatocellular carcinoma cells In Vitro

Takashi Morisaki, Masayo Umebayashi, Akifumi Kiyota, Norihiro Koya, Hiroto Tanaka, Hideya Ohnishi, Mitsuo Katano

研究成果: ジャーナルへの寄稿記事

24 引用 (Scopus)

抄録

Aim: Sorafenib is a promising treatment for hepatocellular carcinoma (HCC) but recent toxicity concerns suggest that new strategies for its use are needed. One approach for reducing toxicity is to use lower doses of sorafenib in combination with other complementary mechanisms. Celecoxib, a cyclooxygenase-2 inhibitor, has been shown to inhibit HCC, and we hypothesized that low-dose sorafenib co-administered with celecoxib could act synergistically in the inhibition of HCC. In this study, the effect of sorafenib was tested in combination with celecoxib on the growth of human HCC cells in vitro. Materials and Methods: Two human HCC cell lines, HepG2 and Huh7, were treated with sorafenib and celecoxib, alone and in combination, and the effect of these treatments on growth, apoptosis, and expression of phospho-AKT was evaluated by WST-8, DNA content, and immunocytochemical assays, respectively. Results: When compared to the actions of either agent alone, the combination of low concentrations of sorafenib (<5 μM) and celecoxib (<20 μM) resulted in enhanced inhibition of both cell growth and AKT activation, and increased the induction of apoptosis. Combination index (CI) analysis showed that the growth inhibition effect was synergistic. Conclusion: This study shows that celecoxib synergistically potentiates the sorafenib-mediated antitumor effect. This finding establishes the foundation for clinical trials evaluating the efficacy of co-administration of soerafenib and celecoxib as a treatment for HCC.

元の言語英語
ページ(範囲)1387-1396
ページ数10
ジャーナルAnticancer Research
33
発行部数4
出版物ステータス出版済み - 4 1 2013

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Celecoxib
Hepatocellular Carcinoma
Growth
Apoptosis
Cyclooxygenase 2 Inhibitors
sorafenib
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Morisaki, T., Umebayashi, M., Kiyota, A., Koya, N., Tanaka, H., Ohnishi, H., & Katano, M. (2013). Combining celecoxib with sorafenib synergistically inhibits hepatocellular carcinoma cells In Vitro. Anticancer Research, 33(4), 1387-1396.

Combining celecoxib with sorafenib synergistically inhibits hepatocellular carcinoma cells In Vitro. / Morisaki, Takashi; Umebayashi, Masayo; Kiyota, Akifumi; Koya, Norihiro; Tanaka, Hiroto; Ohnishi, Hideya; Katano, Mitsuo.

:: Anticancer Research, 巻 33, 番号 4, 01.04.2013, p. 1387-1396.

研究成果: ジャーナルへの寄稿記事

Morisaki, T, Umebayashi, M, Kiyota, A, Koya, N, Tanaka, H, Ohnishi, H & Katano, M 2013, 'Combining celecoxib with sorafenib synergistically inhibits hepatocellular carcinoma cells In Vitro', Anticancer Research, 巻. 33, 番号 4, pp. 1387-1396.
Morisaki T, Umebayashi M, Kiyota A, Koya N, Tanaka H, Ohnishi H その他. Combining celecoxib with sorafenib synergistically inhibits hepatocellular carcinoma cells In Vitro. Anticancer Research. 2013 4 1;33(4):1387-1396.
Morisaki, Takashi ; Umebayashi, Masayo ; Kiyota, Akifumi ; Koya, Norihiro ; Tanaka, Hiroto ; Ohnishi, Hideya ; Katano, Mitsuo. / Combining celecoxib with sorafenib synergistically inhibits hepatocellular carcinoma cells In Vitro. :: Anticancer Research. 2013 ; 巻 33, 番号 4. pp. 1387-1396.
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AU - Tanaka, Hiroto

AU - Ohnishi, Hideya

AU - Katano, Mitsuo

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