PMID- 23749906 OWN - NLM STAT- MEDLINE DCOM- 20130813 LR - 20210223 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 33 IP - 6 DP - 2013 Jun TI - Cannabinoid receptor agonist as an alternative drug in 5-fluorouracil-resistant gastric cancer cells. PG - 2541-7 AB - 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. FAU - Xian, Xiang-Shu AU - Xian XS AD - Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Park, Hyeyeon AU - Park H FAU - Choi, Myung-Gyu AU - Choi MG FAU - Park, Jae Myung AU - Park JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Antimetabolites, Antineoplastic) RN - 0 (Antineoplastic Agents) RN - 0 (Benzoxazines) RN - 0 (Cannabinoid Receptor Agonists) RN - 0 (Morpholines) RN - 0 (Naphthalenes) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Receptors, Cannabinoid) RN - 0 (bcl-2-Associated X Protein) RN - 5H31GI9502 ((3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 3.4.22.- (Caspase 3) RN - U3P01618RT (Fluorouracil) SB - IM MH - Antimetabolites, Antineoplastic/pharmacology MH - Antineoplastic Agents/pharmacology MH - Apoptosis/drug effects MH - Benzoxazines/*pharmacology MH - Cannabinoid Receptor Agonists/*pharmacology MH - Caspase 3/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Drug Resistance, Neoplasm MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Fluorouracil/pharmacology MH - Humans MH - Morpholines/*pharmacology MH - Naphthalenes/*pharmacology MH - Poly(ADP-ribose) Polymerases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Receptors, Cannabinoid/*metabolism MH - Stomach Neoplasms/*drug therapy MH - bcl-2-Associated X Protein/metabolism OTO - NOTNLM OT - Gastric cancer OT - apoptosis OT - cannabinoids OT - drug resistance OT - fluorouracil EDAT- 2013/06/12 06:00 MHDA- 2013/08/14 06:00 CRDT- 2013/06/11 06:00 PHST- 2013/06/11 06:00 [entrez] PHST- 2013/06/12 06:00 [pubmed] PHST- 2013/08/14 06:00 [medline] AID - 33/6/2541 [pii] PST - ppublish SO - Anticancer Res. 2013 Jun;33(6):2541-7.