Cannabinoids Inhibited Pancreatic Cancer via P-21 Activated Kinase 1 Mediated Pathway
| Autor: | Kai Wang, Nhi Huynh, Chelsea Dumesny, Hong S. He, Yang Yang, Mehrdad Nikfarjam |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Apoptosis lcsh:Chemistry Mice Tumor Cells Cultured Dronabinol lcsh:QH301-705.5 Spectroscopy Mice Knockout Kinase Chemistry Pancreatic Stellate Cells General Medicine Computer Science Applications surgical procedures operative CBD medicine.drug PDA PD-L1 Stromal cell THC digestive system Catalysis Article Inorganic Chemistry mental disorders medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology Cell Proliferation Cell growth Cannabinoids organic chemicals Organic Chemistry Immune checkpoint digestive system diseases Mice Inbred C57BL Pancreatic Neoplasms lcsh:Biology (General) lcsh:QD1-999 p21-Activated Kinases Cell culture Hepatic stellate cell Cancer research PAK1 Hallucinogens Cannabidiol |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 21 International Journal of Molecular Sciences, Vol 21, Iss 8035, p 8035 (2020) |
| ISSN: | 1422-0067 |
| Popis: | The anti-cancer effects of cannabinoids including CBD (Cannabidiol) and THC ((&minus )-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. |
| Databáze: | OpenAIRE |
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