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Synergistic Effect of Bazedoxifene and PARP Inhibitor in the Treatment of Ovarian Cancer Regardless of BRCA Mutation

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单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Thorac Surg, Tongji Med Coll, Wuhan, Peoples R China [2]Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA
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关键词: Key Words PARP talazoparib IL-6 inhibitor bazedoxifene BRCA ovarian cancer

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Background/Aim: Poly (ADP-ribose) polymerase inhibitors (PARPis) are one of the targeted therapies proven to treat breast cancer gene (BRCA)-mutant ovarian cancer. Because most ovarian cancers are BRCA wild-type, it is necessary to extend the usage of PARPis. In the present study, we combined the PARPi, talazoparib, and the IL-6 inhibitor, bazedoxifene, for the treatment of human ovarian cancer cells. Materials and Methods: The human ovarian cancer cell lines, SKOV3, UWB1.289 (BRCA1-null) and OV75, were treated with talazoparib and bazedoxifene, as monotherapy or combination treatment. The effects of treatment on cell viability, migration, growth and colony formation were examined. Western blot was used to investigate pathways that may be involved in the antitumor effects of the two agents. Results: The combination of talazoparib and bazedoxifene showed synergistic inhibition of cell viability, cell migration, cell growth, and cell colony formation on all the studied cell lines. The expression of p-AKT, c-myc, p-ERK, ER alpha was inhibited, and gamma-H2AX expression was induced. Conclusion: Combined inhibition of PARP and IL-6 may be an efficacious treatment for ovarian cancer, independently of BRCA mutation status.

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出版当年[2020]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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Q4 ONCOLOGY
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Q4 ONCOLOGY

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Thorac Surg, Tongji Med Coll, Wuhan, Peoples R China [2]Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA
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