trichostatin-a and Laryngeal-Neoplasms

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.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Synergism; Epithelial-Mesenchymal Transition; Genistein; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Laryngeal Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction

To explore the effects of 5-Aza-2'-deoxycitydine(5-Aza-dC) and trichostatin A (TSA) on the expression and methylation of CHFR in human laryngeal carcinoma cell line.. The mRNA expression and promoter hypermethylation and were detected by Realtime fluro-genetic quantitative PCR and methylation specific PCR in Hep-2 cell line, which were cultured in vitro and then treated with different concentrations of 5-Aza-dC and TSA.. Compared with the control team, 5-Aza-dC alone reactivated expression of the CHFR in Hep-2 cell line (1.75 +/- 0.21). TSA had no effect on gene expression (1.05 +/- 0.13). The combined treatment with 5-Aza-dC and TSA increased gene expression (2.15 +/- 0.18). The cell lines showed a characteristic DNA methylation status. 5-Aza-dC and combined 5-Aza-dC and TSA resulted in demethylation of CHFR. In contrast, TSA alone did not affect the DNA methylation status of CHFR.. Hypermethylation of CHFR gene promoter is a common event in the occurrence and development of laryngeal carcinoma. The promoter aberrant methylation of CHFR is a main cause for down-expression of CHFR. After either treatment with 5-Aza-dC alone or in combination with TSA, the expression of CHFR is up-regulated duo to the reversal methylation. It can be a new idea to the therapy of laryngeal carcinoma.

Topics: Azacitidine; Cell Cycle Proteins; Decitabine; DNA Methylation; Gene Expression; Hep G2 Cells; Humans; Hydroxamic Acids; Laryngeal Neoplasms; Methylation; Neoplasm Proteins; Poly-ADP-Ribose Binding Proteins; Promoter Regions, Genetic; Ubiquitin-Protein Ligases