title: Cannabinoid receptor agonist as an alternative drug in 5-fluorouracil-resistant gastric cancer cells.
abstract: Fluorouracil is the main chemotherapeutic drug used for gastrointestinal cancers, which suffers the important problem of treatment resistance. There is little information whether cannabinoid agonists can be used as an alternative drug for fluorouracil-resistant gastric cancer cells. In this study, we investigated the effects of a cannabinoid agonist, WIN-55,212-2, on 5-fluorouracil (5-FU)-resistant human gastric cancer cells, to examine whether the cannabinoid agonist may be an alternative therapy. Survival of the 5-FU-resistant gastric cancer cell line, SNU-620-5FU/1000, was not significantly reduced even by a high dose of 5-FU treatment. However, WIN-55,212-2 inhibited the proliferation of SNU-620-5FU/1000 and enhanced their apoptosis, as indicated by an increase of apoptotic cell proportion, activated caspase-3 and Poly (ADP-ribose) polymerase cleavage. Furthermore, WIN-55,212-2 reduced phospho-extracellular-signal-regulated kinases (ERK) 1/2, phospho-Akt (protein kinase B), B-cell lymphoma-2 (BCL2) and BCL2-associated X (BAX) protein expression in 5-FU-resistant gastric cancer cells. These results indicate that a cannabinoid agonist may, indeed, be an alternative chemotherapeutic agent for 5-FU-resistant gastric cancer.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Xiang-Shu
authors.initials: XS
authors.lastname: Xian
authors.forename: Hyeyeon
authors.initials: H
authors.lastname: Park
authors.forename: Myung-Gyu
authors.initials: MG
authors.lastname: Choi
authors.forename: Jae Myung
authors.initials: JM
authors.lastname: Park
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D048588:Benzoxazines / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; D019253:Proto-Oncogene Proteins c-bcl-2; D043882:Receptors, Cannabinoid; D051028:bcl-2-Associated X Protein; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D005472:Fluorouracil
keywords: Gastric cancer; apoptosis; cannabinoids; drug resistance; fluorouracil