Combination of azacitidine and trichostatin A decreased the tumorigenic potential of lung cancer cells

Purpose This study aims to investigate the possibility of using epigenetic inhibitors against lung cancer. Methods The changes in the proliferation of human lung cancer cells, NCI-H1975 and NCI-H1299 cells, treated with various doses of inhibitors of DNA methyltransferase (azacitidine [5-AZA]) or histone deacetylase inhibitors (trichostatin A [TSA]) were determined by cell counting. The cell viability of NCI-H1975 and NCI-H1299 cells treated with 5-AZA and/or TSA was measured by the MTT assay. The changes in expression of the AKT signaling pathway molecules caused by the application of 5-AZA and TSA were analyzed through their protein and mRNA levels. A xenograft model was used to observe the effects of 5-AZA and TSA on tumor growth in vivo. Results 5-AZA and TSA inhibited the proliferation and viability of NCI-H1975 and NCI-H1299 cells. Their joint application significantly influenced the expression of key molecules in AKT signaling pathway in vitro, and inhibited the growth of xenograft tumors in vivo. Furthermore, TSA and 5-AZA decreased the tumorigenic ability of NCI-H1975 cells in vivo. Conclusion The decreased cell viability and tumorigenic ability, as well as increased anti-oncogene expression following the joint application of 5-AZA and TSA, make these epigenetic inhibitors prospective therapeutic agents for lung cancer.

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