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

  • Authors:
    • Zhengyi Luo
    • Jiafeng Wang
    • Chenglin Li
    • Yumiao Qiu
    • Jing Huang
    • Yujie Huang
    • Hongli Gu
    • Bin Wu
    • Zhe Hu
    • Yan Zhen
  • View Affiliations

  • Published online on: February 8, 2018     https://doi.org/10.3892/mmr.2018.8585
  • Pages: 5996-6001
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

4-aminopyridine (4-AP), a voltage-gated potassium channel blocker, was revealed to possess pro‑apoptotic properties in various types of cancer cells. The present study aimed to explore the effect of 4‑AP 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 4‑AP inhibited cell growth in vitro and a tumorigenesis assay in nude mice determined that 4‑AP also inhibited cell growth in vivo. 4‑AP induced cell apoptosis of A549/CDDP cells observed by electron microscopy and Annexin V‑APC/7‑ADD analysis. In addition, 4‑AP enhanced the sensitivity of A549/CDDP cells to DDP as revealed by an MTT assay. Mechanistically, 4‑AP upregulated the phosphatase and tensin homolog (PTEN) and modulated the phosphoinositide 3‑kinase/protein kinase B signaling pathway and its downstream cell cycle factors, including cyclin D1, cyclin‑dependent kinase 4 and p21, as well as apoptosis‑associated proteins B‑cell lymphoma 2, pro‑caspase 9, pro‑caspase 3, cleaved caspase 9 and cleaved caspase 3. The effects of 4‑AP on cell growth and apoptosis were reversed by PTEN silencing. In conclusion, the results indicated that 4‑AP inhibited cell growth, induced apoptosis and sensitized A549/CDDP cells to DDP via the upregulation of PTEN. 4‑AP may be a potential therapeutic agent for patients with DDP resistance.
View Figures
View References

Related Articles

Journal Cover

April-2018
Volume 17 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Luo Z, Wang J, Li C, Qiu Y, Huang J, Huang Y, Gu H, Wu B, Hu Z, Zhen Y, Zhen Y, et al: Upregulation of phosphatase and tensin homolog is essential for the effect of 4-aminopyridine on A549/CDDP cells. Mol Med Rep 17: 5996-6001, 2018.
APA
Luo, Z., Wang, J., Li, C., Qiu, Y., Huang, J., Huang, Y. ... Zhen, Y. (2018). Upregulation of phosphatase and tensin homolog is essential for the effect of 4-aminopyridine on A549/CDDP cells. Molecular Medicine Reports, 17, 5996-6001. https://doi.org/10.3892/mmr.2018.8585
MLA
Luo, Z., Wang, J., Li, C., Qiu, Y., Huang, J., Huang, Y., Gu, H., Wu, B., Hu, Z., Zhen, Y."Upregulation of phosphatase and tensin homolog is essential for the effect of 4-aminopyridine on A549/CDDP cells". Molecular Medicine Reports 17.4 (2018): 5996-6001.
Chicago
Luo, Z., Wang, J., Li, C., Qiu, Y., Huang, J., Huang, Y., Gu, H., Wu, B., Hu, Z., Zhen, Y."Upregulation of phosphatase and tensin homolog is essential for the effect of 4-aminopyridine on A549/CDDP cells". Molecular Medicine Reports 17, no. 4 (2018): 5996-6001. https://doi.org/10.3892/mmr.2018.8585