Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/18131
Title: Inhibition of p21 activated kinase enhances tumour immune response and sensitizes pancreatic cancer to gemcitabine.
Authors: Wang, Kai;Huynh, Nhi;Wang, Xiao;Baldwin, Graham S;Nikfarjam, Mehrdad;He, Hong
Affiliation: Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: Jan-2018
EDate: 2017-11-07
Citation: International journal of oncology 2018; 52(1): 261-269
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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/18131
DOI: 10.3892/ijo.2017.4193
ORCID: 0000-0002-0944-8747
0000-0003-4866-276X
PubMed URL: 29115428
Type: Journal Article
Appears in Collections:Journal articles

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