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Cannabidiol Suppresses EMT in Pancreatic Cancer via Inhibition of MALAT1 lncRNA and PI3K/Akt/mTOR Signaling Pathway

Na Young Kim1, Young Yun Jung1, Jae-Young Um1,2

  • 1Department of Science in Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

IUBMB Life
|August 6, 2025
PubMed

Insights

Cannabidiol (CBD) inhibits pancreatic cancer metastasis by suppressing epithelial-mesenchymal transition (EMT) and key signaling pathways. CBD also enhances chemotherapy effectiveness, offering a promising therapeutic strategy for pancreatic ductal adenocarcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) exhibits aggressive metastasis and chemoresistance, driven by epithelial-mesenchymal transition (EMT) and chemokine signaling.
  • The therapeutic potential of Cannabidiol (CBD) in PDAC is recognized, but its specific mechanisms in regulating EMT require further elucidation.

Purpose of the Study:

  • To investigate the effects of CBD on EMT, metastasis, and related signaling pathways in PDAC cells.
  • To explore the potential of CBD as an adjunct therapy with gemcitabine for PDAC treatment.

Main Methods:

  • Assessed the impact of CBD on cell migration, invasion, EMT markers (mesenchymal and epithelial), and chemokine receptors (CXCR4/CXCR7) in PDAC cell lines (MIA PaCa-2, PANC-1, AsPC-1).
  • Investigated CBD's effect on the long non-coding RNA MALAT1 and the PI3K/Akt/mTOR pathway.
  • Evaluated the synergistic effects of CBD combined with gemcitabine on PDAC cells.

Main Results:

  • CBD significantly suppressed PDAC cell migration and invasion by downregulating CXCR4/CXCR7, MMP-2/9, and reversing CXCL12-induced EMT.
  • CBD inhibited MALAT1 expression and its pro-invasive effects, while also reversing MALAT1-induced activation of the PI3K/Akt/mTOR pathway and EMT markers.
  • The combination of CBD and gemcitabine demonstrated synergistic inhibition of MALAT1, EMT markers, and the PI3K/Akt/mTOR pathway without added cytotoxicity.

Conclusions:

  • CBD effectively impedes PDAC metastasis by inhibiting EMT and related signaling pathways, including MALAT1 and PI3K/Akt/mTOR.
  • CBD shows promise as a complementary therapeutic agent, enhancing the efficacy of gemcitabine in PDAC treatment.
Keywords:
EMTMALAT1 lncRNAPI3K/Akt/mTORcannabidiolpancreatic cancer

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