Preprint Article Version 1 This version is not peer-reviewed

The PAK Inhibitor PF-3758309 Promotes the Inhibitory Effects of Multiple Chemotherapeutic Reagents on Patient-Derived Pancreatic Cancer Cell Lines

Version 1 : Received: 17 September 2018 / Approved: 17 September 2018 / Online: 17 September 2018 (15:28:54 CEST)

How to cite: Wang, K.; Huynh, N.; Wang, X.; Pajic, M.; Parkin, A.; Man, J.; Baldwin, G.; He, H.; Nikfarjam, M. The PAK Inhibitor PF-3758309 Promotes the Inhibitory Effects of Multiple Chemotherapeutic Reagents on Patient-Derived Pancreatic Cancer Cell Lines. Preprints 2018, 2018090322 (doi: 10.20944/preprints201809.0322.v1). Wang, K.; Huynh, N.; Wang, X.; Pajic, M.; Parkin, A.; Man, J.; Baldwin, G.; He, H.; Nikfarjam, M. The PAK Inhibitor PF-3758309 Promotes the Inhibitory Effects of Multiple Chemotherapeutic Reagents on Patient-Derived Pancreatic Cancer Cell Lines. Preprints 2018, 2018090322 (doi: 10.20944/preprints201809.0322.v1).

Abstract

Pancreatic ductal adenocarcinoma (PDA) remains the most lethal malignancy due to lack of an effective treatment. P21-activated kinases (PAKs) play key roles in PDA growth, and the PAK inhibitor PF-3758309 synergistically reduced PDA growth with gemcitabine. The aim of this study was to determine the effect of PF-3758309 with multiple chemotherapeutic reagents on a panel of patient-derived PDA cell lines. Cells were treated with PF-3758309 plus or minus gemcitabine, 5-fluorouracil (5-FU) or abraxane, and cell proliferation was determined. Protein expression profiles were measured by Western blot. PDA cells were subcutaneously injected into the flanks of SCID mice which were then treated with PF-3758309, gemcitabine, PF-3758309 plus gemcitabine, or gemcitabine plus abraxane. Tumour growth was measured by volume and weight. PF-3758309 enhanced the inhibitory effects of 5-FU, gemcitabine and abraxane on a panel of patient-derived PDA cells, inhibited HIF-1 protein expression and reduced the protein levels of palladin and -SMA in these cells. The combination of PF-3758309 with gemcitabine maximally inhibited PDA growth in vivo, which was comparable to the combination of gemcitabine with abraxane. PF-3758309 enhanced the suppressive effects of multiple chemotherapeutic reagents on the growth of a panel of patient-derived PDA cell lines. The combination of PF-3758309 with gemcitabine provides a potential treatment option with less toxicity than gemcitabine plus abraxane.

Subject Areas

p21-activated kinase (PAK); Pancreatic ductal adenocarcinoma (PDA); PF-3758309; gemcitabine

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.