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dc.contributor.authorYang, Y
dc.contributor.authorNhi, H
dc.contributor.authorDumesny, C
dc.contributor.authorWang, K
dc.contributor.authorHe, H
dc.contributor.authorNikfarjam, M
dc.date.accessioned2020-12-09T22:27:16Z
dc.date.available2020-12-09T22:27:16Z
dc.date.issued2020-11-01
dc.identifierpii: ijms21218035
dc.identifier.citationYang, Y., Nhi, H., Dumesny, C., Wang, K., He, H. & Nikfarjam, M. (2020). Cannabinoids Inhibited Pancreatic Cancer via P-21 Activated Kinase 1 Mediated Pathway. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (21), https://doi.org/10.3390/ijms21218035.
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/11343/252969
dc.description.abstractThe 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.
dc.languageEnglish
dc.publisherMDPI
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleCannabinoids Inhibited Pancreatic Cancer via P-21 Activated Kinase 1 Mediated Pathway
dc.typeJournal Article
dc.identifier.doi10.3390/ijms21218035
melbourne.affiliation.departmentSurgery (Austin & Northern Health)
melbourne.affiliation.departmentSurgery (RMH)
melbourne.source.titleInternational Journal of Molecular Sciences
melbourne.source.volume21
melbourne.source.issue21
dc.rights.licenseCC BY
melbourne.elementsid1478606
melbourne.contributor.authorNikfarjam, Mehrdad
melbourne.contributor.authorHe, Hong
melbourne.contributor.authorDumesny, Chelsea
melbourne.contributor.authorYang, Yang
melbourne.contributor.authorWang, Kai
dc.identifier.eissn1422-0067
melbourne.accessrightsOpen Access


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