Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
April-2018 Volume 17 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2018 Volume 17 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

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 / Copyright

    Affiliations: Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
  • Pages: 5996-6001
    |
    Published online on: February 8, 2018
       https://doi.org/10.3892/mmr.2018.8585
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Califano R, Karamouzis MV, Banerjee S, de Azambuja E, Guarneri V, Hutka M, Jordan K, Kamposioras K, Martinelli E, Corral J, et al: Use of adjuvant chemotherapy (CT) and radiotherapy (RT) in incompletely resected (R1) early stage non-small cell lung cancer (NSCLC): A European survey conducted by the European society for medical oncology (ESMO) young oncologists committee. Lung Cancer. 85:74–80. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Stewart DJ: Mechanisms of resistance to cisplatin and carboplatin. Crit Rev Oncol Hematol. 63:12–31. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Chin LS, Park CC, Zitnay KM, Sinha M, DiPatri AJ Jr, Perillán P and Simard JM: 4-Aminopyridine causes apoptosis and blocks an outward rectifier K+ channel in malignant astrocytoma cell lines. J Neurosci Res. 48:122–127. 1997. View Article : Google Scholar : PubMed/NCBI

5 

Kim JA, Kang YS, Jung MW, Kang GH, Lee SH and Lee YS: Ca2+ influx mediates apoptosis induced by 4-aminopyridine, a K+ channel blocker, in HepG2 human hepatoblastoma cells. Pharmacology. 60:74–81. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Wang W, Xiao J, Adachi M, Liu Z and Zhou J: 4-aminopyridine induces apoptosis of human acute myeloid leukemia cells via increasing [Ca2+]i through P2X7 receptor pathway. Cell Physiol Biochem. 28:199–208. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Huang L, Li B, Li W, Guo H and Zou F: ATP-sensitive potassium channels control glioma cells proliferation by regulating ERK activity. Carcinogenesis. 30:737–744. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Dai T, Zhou Q, Zeng X, He J, Yang Y, Li C, Ren D, Liu L and Liao B: A study on the characteristics of the membrane potassium channels in human non-small cell lung cancer cell. Zhongguo Fei Ai Za Zhi. 4:281–286. 2001.(In Chinese). PubMed/NCBI

9 

Zhen Y, Liu Z, Yang H, Yu X, Wu Q, Hua S, Long X, Jiang Q, Song Y, Cheng C, et al: Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma. Cell Death Dis. 4:e8722013. View Article : Google Scholar : PubMed/NCBI

10 

Ru Q, Tian X, Wu YX, Wu RH, Pi MS and Li CY: Voltage-gated and ATP-sensitive K+ channels are associated with cell proliferation and tumorigenesis of human glioma. Oncol Rep. 31:842–848. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Wang H, Wu Q, Liu Z, Luo X, Fan Y, Liu Y, Zhang Y, Hua S, Fu Q, Zhao M, et al: Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. Cell Death Dis. 5:e11552014. View Article : Google Scholar : PubMed/NCBI

12 

Huang L, Wang HY, Li JD, Wang JH, Zhou Y, Luo RZ, Yun JP, Zhang Y, Jia WH and Zheng M: KPNA2 promotes cell proliferation and tumorigenicity in epithelial ovarian carcinoma through upregulation of c-Myc and downregulation of FOXO3a. Cell Death Dis. 4:e7452013. View Article : Google Scholar : PubMed/NCBI

13 

Jiang W, Kahn SM, Zhou P, Zhang YJ, Cacace AM, Infante AS, Doi S, Santella RM and Weinstein IB: Overexpression of cyclin D1 in rat fibroblasts causes abnormalities in growth control, cell cycle progression and gene expression. Oncogene. 8:3447–3457. 1993.PubMed/NCBI

14 

Baldin V, Lukas J, Marcote MJ, Pagano M and Draetta G: Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev. 7:812–821. 1993. View Article : Google Scholar : PubMed/NCBI

15 

Kroemer G, El-Deiry WS, Golstein P, Peter ME, Vaux D, Vandenabeele P, Zhivotovsky B, Blagosklonny MV, Malorni W, Knight RA, et al: Classification of cell death: Recommendations of the nomenclature committee on cell death. Cell Death Differ. 12 Suppl 2:S1463–S1467. 2005. View Article : Google Scholar

16 

Galluzzi L, Maiuri MC, Vitale I, Zischka H, Castedo M, Zitvogel L and Kroemer G: Cell death modalities: Classification and pathophysiological implications. Cell Death Differ. 14:1237–1243. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Cory S and Adams JM: The Bcl2 family: Regulators of the cellular life-or-death switch. Nat Rev Cancer. 2:647–656. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Shi Y: Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell. 9:459–470. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Dong-Dong L, Xi-Ran Z and Xiang-Rong C: Expression and significance of new tumor suppressor gene PTEN in primary liver cancer. J Cell Mol Med. 7:67–71. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Luo H, Yang Y, Duan J, Wu P, Jiang Q and Xu C: PTEN-regulated AKT/FoxO3a/Bim signaling contributes to reactive oxygen species-mediated apoptosis in selenite-treated colorectal cancer cells. Cell Death Dis. 4:e4812013. View Article : Google Scholar : PubMed/NCBI

21 

Florea AM and Büsselberg D: Cisplatin as an anti-tumor drug: Cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel). 3:1351–1371. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
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
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
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team