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Upregulation of phosphatase and tensin homolog is essential for the effect of 4-aminopyridine on A549/CDDP cells.

Mol Med Rep; 17(4): 5996-6001, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29436653
4-aminopyridine (4-AP), a voltage-gated potassium channel blocker, was revealed to possess pro­apoptotic properties in various types of cancer cells. The present study aimed to explore the effect of 4­AP on a cisplatin (DDP) resistant lung cancer cell line A549/CDDP and the underlying mechanism by which it had an effect. In the present study, an MTT assay and cell cycle analysis were used to determine that 4­AP inhibited cell growth in vitro and a tumorigenesis assay in nude mice determined that 4­AP also inhibited cell growth in vivo. 4­AP induced cell apoptosis of A549/CDDP cells observed by electron microscopy and Annexin V­APC/7­ADD analysis. In addition, 4­AP enhanced the sensitivity of A549/CDDP cells to DDP as revealed by an MTT assay. Mechanistically, 4­AP upregulated the phosphatase and tensin homolog (PTEN) and modulated the phosphoinositide 3­kinase/protein kinase B signaling pathway and its downstream cell cycle factors, including cyclin D1, cyclin­dependent kinase 4 and p21, as well as apoptosis­associated proteins B­cell lymphoma 2, pro­caspase 9, pro­caspase 3, cleaved caspase 9 and cleaved caspase 3. The effects of 4­AP on cell growth and apoptosis were reversed by PTEN silencing. In conclusion, the results indicated that 4­AP inhibited cell growth, induced apoptosis and sensitized A549/CDDP cells to DDP via the upregulation of PTEN. 4­AP may be a potential therapeutic agent for patients with DDP resistance.