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    Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells

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    Author
    Cervello, Melchiorre; Bachvarov, Dimcho; Lampiasi, Nadia; Cusimano, Antonella; Azzolina, Antonina; McCubrey, James A.; Montalto, Giuseppe
    Abstract
    Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of the combination, we investigated the expression profile of the combination-treated liver cancer cell lines using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell-cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell lines displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semi-quantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomic analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies.
    URI
    http://hdl.handle.net/10342/7722
    Date
    2013-06-12
    Citation:
    APA:
    Cervello, Melchiorre, & Bachvarov, Dimcho, & Lampiasi, Nadia, & Cusimano, Antonella, & Azzolina, Antonina, & McCubrey, James A., & Montalto, Giuseppe. (June 2013). Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells. , (), - . Retrieved from http://hdl.handle.net/10342/7722

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    MLA:
    Cervello, Melchiorre, and Bachvarov, Dimcho, and Lampiasi, Nadia, and Cusimano, Antonella, and Azzolina, Antonina, and McCubrey, James A., and Montalto, Giuseppe. "Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells". . . (), June 2013. September 25, 2023. http://hdl.handle.net/10342/7722.
    Chicago:
    Cervello, Melchiorre and Bachvarov, Dimcho and Lampiasi, Nadia and Cusimano, Antonella and Azzolina, Antonina and McCubrey, James A. and Montalto, Giuseppe, "Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells," , no. (June 2013), http://hdl.handle.net/10342/7722 (accessed September 25, 2023).
    AMA:
    Cervello, Melchiorre, Bachvarov, Dimcho, Lampiasi, Nadia, Cusimano, Antonella, Azzolina, Antonina, McCubrey, James A., Montalto, Giuseppe. Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells. . June 2013; (): . http://hdl.handle.net/10342/7722. Accessed September 25, 2023.
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