Molecular Medicine Reports, 2016, 13(6):5045-5052.

Trichostatin A potentiates genistein-induced apoptosis and reverses EMT in HEp2 cells

Ruixia DU, Zhe Liu, Xuedong Hou, et al

Department of Otorhinolaryngology, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China; Department of Otorhinolaryngology, Fengtian Hospital, Shenyang Medical University, Shenyang, Liaoning 110024, P.R. China; Department of Pancreatic Surgery, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China

Genistein and trichostatin A (TSA) are two chemotherapeutic compounds with antitumor effects in different types of cancer cell. However, the effects of genistein and TSA on the HEp-2 laryngeal cancer cell line remain to be fully elucidated. In the present study, it was found that genistein and TSA inhibited cell growth and cell migration, and promoted apoptosis in the HEp-2 laryngeal cancer cell line. The HEp-2 cells were treated with genistein, TSA or the two compounds in combination. Cell proliferation and apoptosis were measured using an MTT assay, Annexin V/propidium iodide staining and a TUNEL assay. Cell invasion was determined using a Matrigel-based Transwell assay. Western blotting was used to examine the activation of the Akt pathway and the expression levels of pro-or anti-apoptotic proteins. Treatment with either genistein or TSA alone mildly inhibited cell viability, growth and invasion, and induced the apoptosis of the laryngeal cancer cells, whereas more marked effects were observed in the cells treated with the combination of the two compounds. In addition, genistein reversed endothelial growth factor-induced epithelial-mesenchymal transition (EMT) in the HEp-2 cells, the effect of which were was further increased by joint application with TSA. Treatment of the HEp-2 cells with genistein and TSA led to a significant reduction in the phosphorylation of Akt and activation of its downstream target, and resulted in peroxisome proliferator-activated receptor-γ cleavage, increased expression of B cell lymphoma-2 (Bcl-2)-associated X protein and reduced the expression of Bcl-2. In conclusion, the present study demonstrated that, with the involvement of TSA, genistein exhibited substantial advantages in inhibiting laryngeal carcinoma cell growth, invasion and EMT, and induced apoptosis, compared with genistein treatment alone, which occurred through the regulation of Akt activation and the apoptotic pathway.

中国《分子医学报告》, 2016, 13(6):5045-5052.

在HEp2细胞中曲古霉素A增强染料木黄酮诱导的细胞凋亡并逆转EMT

杜瑞霞，刘哲，候学东，等

中国医科大学附属盛京医院耳鼻咽喉科，辽宁沉阳110004;中国; 沉阳医科大学凤田医院耳鼻咽喉科，辽宁沉阳110024;中国; 中国医科大学第一医院胰腺外科，辽宁沉阳110001