MECHANISMS OF SYNERGISTIC ANTITUMOR EFFECT OF NAPROXEN AND SORAFENIB IN HEPATOCELLULAR CARCINOMA

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2023-1-23

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Akar, Etkin

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Hepatocellular carcinoma (HCC) is life-threatening cancer that accounts for the second leading cause of cancer-related deaths worldwide. Due to the complexity and heterogeneity of HCC, which leads to resistance to current targeted therapies, combination therapy becomes an important strategy. Since 90% of HCC arises from chronic liver inflammation, HCC drugs combined with non-steroid anti- inflammatory drugs (NSAIDs) are considered an important strategy to increase treatment efficacy. In this study, we aimed to find a synergistic interaction between FDA-approved NSAIDs and HCC drugs and investigate the mechanism behind their synergistic interaction. Among all combinations, Naproxen and Sorafenib were found to be synergistically interacting in HCC. Network reconstruction analysis was performed to investigate the mechanism implicated in this drug combination. Apoptosis pathways were enriched in both Sorafenib and Naproxen networks which were further supported by Annexin V/PI staining, Hoechst staining, and analysis of apoptosis-related proteins in HCC cell lines. Our results pointed out that apoptosis induction could be associated with the down-regulation of the CAPN2 gene and decreasing the activity of PI3K/AKT pathway in HCC.

Subject Keywords

HCC, Sorafenib, Naproxen, Synergy, Apoptosis

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https://hdl.handle.net/11511/102087

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

E. Akar, “MECHANISMS OF SYNERGISTIC ANTITUMOR EFFECT OF NAPROXEN AND SORAFENIB IN HEPATOCELLULAR CARCINOMA,” M.S. - Master of Science, Middle East Technical University, 2023.