Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, 02-097 Warsaw, Poland.
Oncol Rep. 2018 Apr;39(4):1999-2005. doi: 10.3892/or.2018.6248. Epub 2018 Feb 6.
Despite debulking surgery and good initial response to chemotherapy, the majority of patients with advanced ovarian cancer relapse and succumb to their disease. Thus, there is a pressing need to improve treatment outcome. In the present study, the antitumor activity of histone deacetylase (HDAC) inhibitor scriptaid in combination with bortezomib or conventional chemotherapeutics was tested in vitro against representative ovarian cancer cell lines: SKOV‑3, MDAH 2774, and OVP‑10. Incubation of ovarian cancer cells with scriptaid and bortezomib (or doxorubicin) led to synergistic antitumor effects. As shown in the Annexin V-FITC/PI assay and western blot analysis of caspase‑3/-9 and p21 protein expression, these synergistic antitumor effects were due to both induction of apoptosis and inhibition of proliferation. Since synergistic antitumor activity of scriptaid and bortezomib appeared in suboptimal concentrations, one can assume that the administration of the combination of these agents to ovarian cancer patients can exert the therapeutic effect in parallel with limited general toxicity of the treatment.
尽管进行了肿瘤减灭术和对化疗的良好初始反应，大多数晚期卵巢癌患者仍会复发并死于该疾病。因此，迫切需要改善治疗效果。在本研究中，体外检测了组蛋白去乙酰化酶（HDAC）抑制剂 scriptaid 与硼替佐米或常规化疗药物联合用于代表性卵巢癌细胞系：SKOV-3、MDAH 2774 和 OVP-10 的抗肿瘤活性。scriptaid 和硼替佐米（或多柔比星）孵育卵巢癌细胞导致协同抗肿瘤作用。如 Annexin V-FITC/PI 检测和 caspase-3/-9 和 p21 蛋白表达的 Western blot 分析所示，这些协同抗肿瘤作用归因于凋亡诱导和增殖抑制。由于 scriptaid 和硼替佐米的协同抗肿瘤活性出现在亚最佳浓度下，因此可以假设将这些药物联合用于卵巢癌患者的治疗可以在有限的治疗全身毒性的情况下发挥治疗作用。
