Cannabinoid receptor agonist as an alternative drug in 5-fluorouracil-resistant gastric cancer cells

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, w...

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Bibliographic Details
Published in:Anticancer research 2013-06, Vol.33 (6), p.2541
Main Authors: Xian, Xiang-Shu, Park, Hyeyeon, Choi, Myung-Gyu, Park, Jae Myung
Format: Article
Language:English
Subjects:
Antimetabolites, Antineoplastic - pharmacology
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
bcl-2-Associated X Protein - metabolism
Benzoxazines - pharmacology
Cannabinoid Receptor Agonists - pharmacology
Caspase 3 - metabolism
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
Drug Resistance, Neoplasm
Extracellular Signal-Regulated MAP Kinases - metabolism
Fluorouracil - pharmacology
Humans
Morpholines - pharmacology
Naphthalenes - pharmacology
Poly(ADP-ribose) Polymerases - metabolism
Proto-Oncogene Proteins c-akt - metabolism
Proto-Oncogene Proteins c-bcl-2 - metabolism
Receptors, Cannabinoid - metabolism
Stomach Neoplasms - drug therapy
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Summary: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.
ISSN:1791-7530