Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon 302-120, Republic of Korea.
Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Oncol Rep. 2015 Apr;33(4):1899-907. doi: 10.3892/or.2015.3776. Epub 2015 Feb 2.
Inhibition of histone deacetylases (HDACs) has emerged as a new target for cancer therapies. The present study examined the antitumor effect and molecular mechanism of the HDAC inhibitor apicidin in YD-15 human salivary mucoepidermoid carcinoma (MEC) cells. The cells were treated with apicidin and cell death was quantified using an MTT assay. Apoptosis and autophagy were measured using flow cytometry, immunoblot analysis and cell staining. Regulation of the signaling pathways was monitored using immunoblot analysis and co-treatment with specific inhibitors. Insulin-like growth factor 1 receptor (IGF-1R) was knocked down using specific siRNA. Apicidin significantly inhibited the proliferation of MEC cells. Apicidin also induced apoptosis through the inactivation of extracellular signal-regulated kinase (ERK) and AKT/mTOR signaling and activation of c-Jun NH2-terminal kinase (JNK), whereas apicidin promoted autophagy through inactivation of the AKT/mTOR signaling. These effects may be mediated by the inhibition of IGF-1R, an upstream regulator of MAPK and AKT/mTOR pathways. These results suggested that apicidin is an attractive chemotherapeutic agent against salivary MEC and may be a good candidate for targeting IGF-1R for cancer therapies.
组蛋白去乙酰化酶（HDACs）抑制剂已成为癌症治疗的新靶点。本研究探讨了 HDAC 抑制剂 apicidin 对 YD-15 人涎腺黏液表皮样癌（MEC）细胞的抗肿瘤作用及其分子机制。用 apicidin 处理细胞，并用 MTT 法检测细胞死亡。用流式细胞术、免疫印迹分析和细胞染色法测量细胞凋亡和自噬。用免疫印迹分析和与特定抑制剂的共处理来监测信号通路的调节。使用特异性 siRNA 敲低胰岛素样生长因子 1 受体（IGF-1R）。Apicidin 显著抑制 MEC 细胞的增殖。Apicidin 通过细胞外信号调节激酶（ERK）和 AKT/mTOR 信号的失活以及 c-Jun NH2-末端激酶（JNK）的激活诱导细胞凋亡，而 Apicidin 通过 AKT/mTOR 信号的失活促进自噬。这些作用可能是通过抑制 IGF-1R 介导的，IGF-1R 是 MAPK 和 AKT/mTOR 通路的上游调节剂。这些结果表明，apicidin 是一种有吸引力的涎腺 MEC 化疗药物，可能是针对 IGF-1R 进行癌症治疗的良好候选药物。
