The rationale for developing histone deacetylase (HDAC) inhibitors (HDACi) as anticancer agents was based on their ability to induce apoptosis and cell cycle arrest in cancer cells. However, while HDACi have been remarkably effective in the treatment of hematological malignancies, clinical studies with HDACi as single agents in solid cancers have been disappointing. Recent studies have shown that, in addition to inducing apoptosis in cancer cells, class I HDACi induce IκB kinase (IKK)-dependent expression of proinflammatory chemokines, such as interleukin-8 (IL8; CXCL8), resulting in the increased proliferation of tumor cells, and limiting the effectiveness of HDACi in solid tumors. Here, we discuss the mechanisms responsible for HDACi-induced CXCL8 expression, and opportunities for combination therapies targeting HDACs and IKK in solid tumors.

开发组蛋白脱乙酰基酶（HDAC）抑制剂（HDACi）作为抗癌剂的基本原理是基于其诱导癌细胞凋亡和细胞周期停滞的能力。然而，尽管HDACi在血液系统恶性肿瘤的治疗中非常有效，但将HDACi作为单一药物治疗实体癌的临床研究却令人失望。最近的研究表明，除了诱导癌细胞凋亡外，I类HDACi还诱导IκB激酶（IKK）依赖性的促炎性趋化因子如白介素8（IL8; CXCL8）的表达，从而导致肿瘤细胞增殖增加，并限制了HDACi在实体瘤中的有效性。在这里，我们讨论了负责HDACi诱导的CXCL8表达的机制，以及针对实体瘤中HDAC和IKK的联合疗法的机会。