“Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive metastasis and poor response to chemotherapy, largely driven by epithelial-mesenchymal transition (EMT) and chemokine signaling.
Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has shown anticancer potential, yet its mechanisms in EMT regulation remain underexplored in PDAC.
In this study, we demonstrate that CBD significantly suppresses the expression of CXCR4/CXCR7 and matrix metalloproteinases (MMP-2/9), leading to reduced migration and invasion of MIA PaCa-2, PANC-1, and AsPC-1 cells. Moreover, CBD reversed CXCL12-induced EMT by downregulating mesenchymal markers and restoring epithelial markers. Mechanistically, CBD inhibited the expression of the long non-coding RNA MALAT1, a known EMT regulator, and antagonized its pro-invasive effects. Overexpression of MALAT1 activated the PI3K/Akt/mTOR pathway and enhanced EMT-related protein expression, all of which were effectively reversed by CBD. Furthermore, the combination of CBD and gemcitabine exhibited synergistic inhibition of MALAT1, EMT markers, and PI3K/Akt/mTOR signaling without inducing cytotoxicity, suggesting a therapeutic advantage.
Collectively, these findings reveal a novel mechanism through which CBD impedes PDAC metastasis and underscore its promise as a complementary agent in chemotherapy regimens.”
https://pubmed.ncbi.nlm.nih.gov/40767250/
“Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has garnered considerable interest in oncology for its anti-inflammatory, pro-apoptotic, and anti-metastatic properties.”
“CBD has garnered increasing interest in oncology due to its multifaceted anticancer properties.”