Inhibition of p21 activated kinase enhances tumour immune response and sensitizes pancreatic cancer to gemcitabine

  • Authors:
    • Kai Wang
    • Nhi Huynh
    • Xiao Wang
    • Graham Baldwin
    • Mehrdad Nikfarjam
    • Hong He
  • View Affiliations

  • Published online on: November 7, 2017     https://doi.org/10.3892/ijo.2017.4193
  • Pages:261-269
Metrics: HTML 0 views | PDF 0 views     Cited By: 0 citations

Abstract

Pancreatic ductal adenocarcinoma (PDA) is one of the major types of cancer that exhibit high mortality worldwide because of the late diagnosis and the lack of effective treatment. Immunotherapy appears to be ineffective in PDA treatment due to the existence of a unique immune-suppressive microenvironment in PDA. Gemcitabine-based therapy is still the most commonly used chemotherapy to treat PDA patients with only marginal increased survival rates. This prompted us to continue the search for more effective therapy for PDA treatment. The effects of p21 activated kinases (PAKs) on tumour immune response and gemcitabine response were examined in PDA. An orthotopic murine PDA model, in which pancreatic cancer cells were injected to the tail of pancreas, was used. The mice were treated with PAK inhibitor, PF‑3758309, plus or minus gemcitabine. Tumour growth was measured by volume and weight. Tumour immune response was determined by flow cytometry analysis of splenic cells and immunohistochemical staining of intratumoural lymphocytes. Inhibition of PAKs by PF‑3758309, not only suppressed tumour growth, but also stimulated tumour immune response by increasing the numbers of splenic and intratumoural T lymphocytes. Furthermore, inhibition of PAKs decreased PDA cell growth synergistically with gemcitabine in vitro and in vivo. The dual effects of inhibition of PAKs make PAK-targeted therapy more potent for the treatment of PDA. The combination of PAK inhibitors with gemcitabine may be a more effective therapeutic approach in PDA treatment.

Related Articles

Journal Cover

January 2018
Volume 52 Issue 1

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

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wang, K., Huynh, N., Wang, X., Baldwin, G., Nikfarjam, M., & He, H. (2018). Inhibition of p21 activated kinase enhances tumour immune response and sensitizes pancreatic cancer to gemcitabine. International Journal of Oncology, 52, 261-269. https://doi.org/10.3892/ijo.2017.4193
MLA
Wang, K., Huynh, N., Wang, X., Baldwin, G., Nikfarjam, M., He, H."Inhibition of p21 activated kinase enhances tumour immune response and sensitizes pancreatic cancer to gemcitabine". International Journal of Oncology 52.1 (2018): 261-269.
Chicago
Wang, K., Huynh, N., Wang, X., Baldwin, G., Nikfarjam, M., He, H."Inhibition of p21 activated kinase enhances tumour immune response and sensitizes pancreatic cancer to gemcitabine". International Journal of Oncology 52, no. 1 (2018): 261-269. https://doi.org/10.3892/ijo.2017.4193