[Mechanistic study of nimesulide on enhancing gammadeltaT cell-mediated killing of gastric cancer cells].
OBJECTIVE
To explore the effect of nimesulide on human gammadeltaT cell function.


METHODS
gammadeltaT cells were cultured routinely, collected on the 9th day, and then induced with nimesulide at indicated concentrations (0.25 micromol/L, 0.5 micromol/L, 1 micromol/L, 2 micromol/L, 4 micromol/L, respectively). Twenty-four hours after induction, the supernatants were collected to detect IFN-gamma, TNF-alpha and IL-12, whereas the cells were assayed for perforin, granzyme B and NKG2D by flow cytometry (FCM) and for killing of gastric cancer cells by LDH.


RESULTS
Nimesulide (1 micromol/L) caused gammadeltaT cells to express more of perforin and granzyme B (62.8% and 72.7%, respectively) than the control group (51.4% and 60.9%, respectively) (P<0.05). Likewise, nimesulide (1 micromol/L) enabled gammadeltaT cells to secret more of IFN-gamma and TNF-alpha (262.3 ng/L and 177.5 ng/L, respectively) than the control group (196.1 ng/L and 158.5 ng/L, respectively) (P<0.05). Nimesulide did not affect IL-12 secreting capability of gammadeltaT cells as compared with the control group (P>0.05). Nimesulide-stimulated gammadeltaT cells killed more of SGC-7901 and BCG-823 gastric cancer cells (73% and 70%, respectively) than the control group(54% and 53%, respectively) (P<0.05).


CONCLUSIONS
Nimesulide made gammadeltaT cells to express more perforin and granzyme B and to secret more IFN-gamma and TNF-alpha into the supernatant, leading to higher killing rate of SGC-7901 and BCG-823 gastric cancer cells. The above data provides experimental basis on the clinical use of nimesulide to prevent and treat digestive tract tumors.
Liu
Jun-quan
JQ
Department of Central Laboratory, 97th Hospital of the PLA, Xuzhou, China.
Chen
Fu-xing
FX
Gong
Xin-jian
XJ
Li
Hui-zhong
HZ
Cai
Kai
K
Zhang
Bao-fu
BF
Zhang
Song
S
Zhang
Juan
J
D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D053804:Granzymes / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D054353:Perforin / Q000187:drug effects* / Q000276:immunology; D013274:Stomach Neoplasms / Q000276:immunology*; D013449:Sulfonamides / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes; C012655:nimesulide