Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/25206
Title: Cannabinoids Inhibited Pancreatic Cancer via P-21 Activated Kinase 1 Mediated Pathway.
Austin Authors: Yang, Yang;Huynh, Nhi;Dumesny, Chelsea;Wang, Kai;He, Hong ;Nikfarjam, Mehrdad 
Affiliation: Olivia Newton-John Cancer Research Institute
State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China..
Surgery (University of Melbourne)
Issue Date: 28-Oct-2020
metadata.dc.date: 2020-10-28
Publication information: International Journal of Molecular Sciences 2020; 21(21): 8035
Abstract: The anti-cancer effects of cannabinoids including CBD (Cannabidiol) and THC ((-)-trans-∆9-tetrahydrocannabinol) have been reported in the case of pancreatic cancer (PC). The connection of these cannabinoids to KRas oncogenes that mutate in more than 90% of PC, and their effects on PD-L1, a key target of immune checkpoint blockade, have not been thoroughly investigated. Using cell lines and mouse models of PC, the effects of CBD and THC on cancer growth, the interaction between PC cells and a stromal cell, namely pancreatic stellate cells (PSCs), and the mechanism(s) involved were determined by cell-based assays and mouse study in vivo. CBD and THC inhibited the proliferation of PC, PSC, and PSC-stimulated PC cells. They also suppressed pancreatic tumour growth in mice. Furthermore, CBD and/or THC reduced the expression of PD-L1 by either PC or PSC cells. Knockout of p-21 activated kinase 1 (PAK1, activated by KRas) in PC and PSC cells and, in mice, dramatically decreased or blocked these inhibitory effects of CBD and/or THC. These results indicated that CBD and THC exerted their inhibitions on PC and PSC via a p-21 activated kinase 1 (PAK1)-dependent pathway, suggesting that CBD and THC suppress Kras activated pathway by targeting PAK1. The inhibition by CBD and THC of PD-L1 expression will enhance the immune checkpoint blockade of PC.
URI: https://ahro.austin.org.au/austinjspui/handle/1/25206
DOI: 10.3390/ijms21218035
ORCID: 0000-0002-2342-8750
PubMed URL: 33126623
Type: Journal Article
Subjects: CBD
PAK1
PD-L1
PDA
THC
Appears in Collections:Journal articles

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