BACKGROUND Overexpression of c-Myc is commonly seen in human ovarian cancers, and this could be a potentially novel therapeutic target for this disease. JQ1, a selective small-molecule BET (Bromodomain and extraterminal domain family) bromodomain (BRDs) inhibitor, has been found to suppress tumour progression in several cancer cell types. RESULTS Using a panel of ovarian cancer cell lines and primary cell cultures from human ovarian cancer ascites, we demonstrated that JQ1 significantly suppressed cell proliferation and induced apoptosis in an ovarian cancer cell by targeting BRD4 and c-Μyc. In addition, JQ1 sensitized ovarian cancer cells to cisplatin, the most commonly used chemotherapeutic agent in ovarian cancer. Importantly, this effect was observed in ovarian cells, which exhibited resistance to cisplatin alone. Finally, we show that JQ1 interacts with the JAK-STAT signalling pathway, a pathway important in supporting ovarian cancer cell survival by suppressing or inducing genes involved in cell survival and apoptosis, respectively. CONCLUSION Our data, taken together, suggest that JQ1 is an attractive antitumour candidate for further investigation in the treatment of ovarian cancer, as it associates with cell proliferation, apoptosis, and alterations in the JAK-STAT signalling pathway, especially in patients with a platinum-resistant profile or in patients with relapsed disease.

中文翻译：

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JQ1与顺铂联合抑制肿瘤生长，并抑制卵巢癌的JAK / STAT信号通路。

背景技术c-Myc的过表达在人类卵巢癌中很常见，这可能是该疾病的潜在新治疗靶标。JQ1是一种选择性小分子BET（溴结构域和末端外域家族）溴结构域（BRDs）抑制剂，已发现可以抑制几种癌细胞的肿瘤进展。结果使用一组卵巢癌细胞系和来自人类卵巢癌腹水的原代细胞培养物，我们证明了JQ1通过靶向BRD4和c-Μyc显着抑制卵巢癌细胞的细胞增殖并诱导凋亡。此外，JQ1使卵巢癌细胞对顺铂敏感，顺铂是卵巢癌中最常用的化学治疗剂。重要的是，在仅表现出对顺铂耐药性的卵巢细胞中观察到了这种作用。最后，我们显示JQ1与JAK-STAT信号传导途径相互作用，该途径通过抑制或诱导分别参与细胞存活和凋亡的基因在支持卵巢癌细胞存活中很重要。结论我们的数据合计表明，JQ1是有吸引力的抗肿瘤候选药物，可用于卵巢癌的进一步研究，因为它与细胞增殖，凋亡和JAK-STAT信号通路的改变有关，尤其是铂类患者耐药情况或患有复发性疾病的患者。