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, on5-fluorouracil (5-FU)-resistant human gastric cancer cells, to examine whether the cannabinoid agonist may be an alternative therapy. Survival of the 5-FUresistant 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 phosphoextracellular- signal-regulated kinases (ERK) 1/2, phospho- Akt (protein kinase B), B-cell lymphoma-2 (BCL2) and BCL2-Associated X (BAX) protein expression in5-FUresistant gastric cancer cells. These results indicate that a cannabinoid agonist may, indeed, be an alternative chemotherapeutic agent for 5-FU-resistant gastric cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 2541-2548 |
| Number of pages | 8 |
| Journal | Anticancer Research |
| Volume | 33 |
| Issue number | 6 |
| State | Published - Jun 2013 |
Keywords
- Apoptosis
- Cannabinoids
- Drug resistance
- Fluorouracil
- Gastric cancer
