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The endocannabinoid anandamide inhibits cholangiocarcinoma growth via activation of the noncanonical Wnt signaling pathway
- Source :
- American Journal of Physiology-Gastrointestinal and Liver Physiology. 295:G1150-G1158
- Publication Year :
- 2008
- Publisher :
- American Physiological Society, 2008.
-
Abstract
- Cholangiocarcinomas are cancers that have poor prognosis and limited treatment options. The noncanonical Wnt pathway is mediated predominantly by Wnt 5a, which activates a Ca2+-dependent pathway involving protein kinase C, or a Ca2+-independent pathway involving the orphan receptor Ror2 and subsequent activation of Jun NH2-terminal kinase (JNK). This pathway is associated with growth-suppressing effects in numerous cell types. We have shown that anandamide decreases cholangiocarcinoma growth in vitro. Therefore, we determined the effects of anandamide on cholangiocarcinoma tumor growth in vivo using a xenograft model and evaluated the effects of anandamide on the noncanonical Wnt signaling pathways. Chronic administration of anandamide decreased tumor growth and was associated with increased Wnt 5a expression in vitro and in vivo. Treatment of cholangiocarcinoma cells with recombinant Wnt 5a decreased cell proliferation in vitro. Neither anandamide nor Wnt 5a affected intracellular calcium release, but both increased the JNK phosphorylation. Stable knockdown of Wnt 5a or Ror2 expression in cholangiocarcinoma cells abolished the effects of anandamide on cell proliferation and JNK activation. Modulation of the endocannabinoid system may be important in cholangiocarcinoma treatment. The antiproliferative actions of the noncanonical Wnt signaling pathway warrants further investigation to dissect the mechanism by which this may occur.
- Subjects :
- Male
medicine.medical_specialty
receptor tyrosine kinase orphan receptor 2
Polyunsaturated Alkamides
Physiology
medicine.medical_treatment
Mice, Nude
Arachidonic Acids
Biology
Wnt-5a Protein
jun nh 2-terminal kinase
Cholangiocarcinoma
Mice
chemistry.chemical_compound
Cell Line, Tumor
Proto-Oncogene Proteins
biliary tract cancer
Physiology (medical)
Internal medicine
Cannabinoid Receptor Modulators
medicine
Animals
Humans
Cell Proliferation
jun nh(2)-terminal kinase
Mice, Inbred BALB C
Hepatology
Gastroenterology
Wnt signaling pathway
LRP6
LRP5
Anandamide
Endocannabinoid system
Wnt Proteins
Liver and Biliary Tract
Endocrinology
chemistry
Trk receptor
Cancer research
Cannabinoid
Signal transduction
Neoplasm Transplantation
Endocannabinoids
Signal Transduction
Subjects
Details
- ISSN :
- 15221547 and 01931857
- Volume :
- 295
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Accession number :
- edsair.doi.dedup.....58a2870a32880a2ab7e6284f5b22b983