Inhibition of p21-activated kinase 4 expression suppresses the proliferation of Hep-2 laryngeal carcinoma cells via activation of the ATM/Chk1/2/p53 pathway

  • Authors:
    • Xin Sun
    • Bin Liu
    • Jin Wang
    • Jun Li
    • Wen-Yue Ji
  • View Affiliations

  • Published online on: November 29, 2012     https://doi.org/10.3892/ijo.2012.1718
  • Pages: 683-689
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

In the present study, we investigated the effects of the p21-activated kinase 4 (Pak4) gene on Hep-2 laryngeal carcinoma cells in vivo and in vitro. The expression of Pak4 was downregulated using small interfering RNA (siRNA). The downregulation of Pak4 decreased the proliferation and increased apoptosis and S phase arrest in Hep-2 cells in vitro. In further experiments, we determined that the S/G2 transition was obstructed by the downregulation of Pak4 using 5‑chloro-2'‑deoxyuridine (CldU) and 5‑iodo‑2'‑deoxyuridine (IdU) double staining. A xenografted Hep-2 tumor mouse model was created by inducing human tumors with a subcutaneous (s.c.) injection of 5x106 Hep-2 cells into the dorsal flank region of nu̸nu mice. The downregulation of Pak4 in established xenografted tumors decreased tumor size and weight. The survival rate of the mice with tumors that did not express Pak4 was significantly higher compared to the mice with tumors expressing Pak4. These results confirm the role of Pak4 as an oncogene in laryngeal carcinoma cells. To identify the mechanism of the cell cycle arrest induced by Pak4, immunohistochemical staining was performed to detect changes in cell cycle‑related proteins. The results demonstrated that p53 was activated following the downregulation of Pak4. The levels of ataxia telangiectasia mutated (ATM), the upstream protein of checkpoint kinase (Chk)1 and Chk2, also increased. Therefore, we confirmed that the mechanisms of the Pak4-induced cell cycle arrest invovlve the activation of the ATM/Chk1/2/p53 pathway. These results may prove helpful for the development of novel therapies for the treatment of laryngeal carcinoma.
View Figures
View References

Related Articles

Journal Cover

February 2013
Volume 42 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Sun, X., Liu, B., Wang, J., Li, J., & Ji, W. (2013). Inhibition of p21-activated kinase 4 expression suppresses the proliferation of Hep-2 laryngeal carcinoma cells via activation of the ATM/Chk1/2/p53 pathway. International Journal of Oncology, 42, 683-689. https://doi.org/10.3892/ijo.2012.1718
MLA
Sun, X., Liu, B., Wang, J., Li, J., Ji, W."Inhibition of p21-activated kinase 4 expression suppresses the proliferation of Hep-2 laryngeal carcinoma cells via activation of the ATM/Chk1/2/p53 pathway". International Journal of Oncology 42.2 (2013): 683-689.
Chicago
Sun, X., Liu, B., Wang, J., Li, J., Ji, W."Inhibition of p21-activated kinase 4 expression suppresses the proliferation of Hep-2 laryngeal carcinoma cells via activation of the ATM/Chk1/2/p53 pathway". International Journal of Oncology 42, no. 2 (2013): 683-689. https://doi.org/10.3892/ijo.2012.1718