Combination of azacitidine and trichostatin A decreased the tumorigenic potential of lung cancer cells.
Combination of azacitidine and trichostatin A decreased the tumorigenic potential of lung cancer cells.
复制标题
阿扎胞苷和曲古抑菌素 A 的组合降低了肺癌细胞的致瘤潜力
DOI：
10.2147/ott.s136218
复制
发表时间：
2017
影响因子：
4
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Yang Y;Yin W;Wu F;Fan J
本研究旨在探讨表观遗传抑制剂治疗肺癌的可能性。用细胞计数法测定不同剂量的DNA甲基转移酶抑制剂（阿扎胞苷[5-AZA]）或组蛋白脱乙酰酶抑制剂（阿司他丁A [TSA]）处理人肺癌细胞NCI-H1975和NCI-H1299细胞后细胞增殖的变化。通过MTT测定来测量用5-AZA和/或TSA处理的NCI-H1975和NCI-H1299细胞的细胞活力。通过蛋白质和mRNA水平分析了5-AZA和TSA应用引起的AKT信号通路分子表达的变化。采用裸鼠移植瘤模型，观察5-AZA和TSA对裸鼠移植瘤生长的影响。5-AZA和TSA可抑制NCI-H1975和NCI-H1299细胞的增殖和活力。联合应用可显著影响体外AKT信号通路中关键分子的表达，抑制体内异种移植瘤的生长。TSA和5-AZA可降低NCI-H1975细胞的体内致瘤能力。5-AZA和TSA联合应用后细胞活力和致瘤能力降低，抑癌基因表达增加，使这些表观遗传抑制剂成为肺癌的潜在治疗药物。
This study aims to investigate the possibility of using epigenetic inhibitors against lung cancer. 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. 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. 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.