• Takashi Morisaki, Masayo Umebayashi, Akifumi Kiyota, Norihiro Koya, Hiroto Tanaka, Hideya Onishi, and Mitsuo Katano.
• Fukuoka General Cancer Clinic, Fukuoka, Japan. tmorisaki@cancer-clinic.jp
• Anticancer Res. 2013 Apr 1; 33 (4): 1387-95.

AimSorafenib 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 MethodsTwo 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.ResultsWhen 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.ConclusionThis 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.

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