Zhang Ruijie, Wang Tiffany, Lin Jiayuh
Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, U.S.A.
Anticancer Res. 2021 May;41(5):2277-2286. doi: 10.21873/anticanres.15003.
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.
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.
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, ERα was inhibited, and γ-H2AX expression was induced.
Combined inhibition of PARP and IL-6 may be an efficacious treatment for ovarian cancer, independently of BRCA mutation status.
背景/目的：聚（ADP - 核糖）聚合酶抑制剂（PARPis）是经证实可治疗乳腺癌基因（BRCA）突变型卵巢癌的靶向治疗药物之一。由于大多数卵巢癌为BRCA野生型，因此有必要扩大PARPis的应用范围。在本研究中，我们将PARPi他拉唑帕尼与白细胞介素-6抑制剂巴多昔芬联合用于治疗人卵巢癌细胞。
用人卵巢癌细胞系SKOV3、UWB1.289（BRCA1缺失）和OV75，分别采用他拉唑帕尼和巴多昔芬单药治疗或联合治疗。检测治疗对细胞活力、迁移、生长和集落形成的影响。采用蛋白质免疫印迹法研究这两种药物抗肿瘤作用可能涉及的信号通路。
他拉唑帕尼与巴多昔芬联合用药对所有研究的细胞系均显示出对细胞活力、细胞迁移、细胞生长和细胞集落形成的协同抑制作用。p - AKT、c - myc、p - ERK、ERα的表达受到抑制，γ - H2AX表达被诱导。
联合抑制PARP和白细胞介素-6可能是一种治疗卵巢癌的有效方法，与BRCA突变状态无关。
