[Effects of EGFR inhibitor AG1478 in combination with celecoxib on the growth of gastric cancer cells].
OBJECTIVE
To investigate whether EGFR inhibitor AG1478 combined with celecoxib could enhance the inhibitive effects on the growth of gastric cancer cells.


METHODS
Human gastric cancer cell line SGC-7901 was cultured and treated with different concentration of AG1478 and celecoxib, the proliferation of SGC-7901 cells was determined by MTT. The expression of proliferation cell nuclear antigen (PCNA) of SGC-7901 cells was detected by immunocytochemistry. ERK and p-ERK expression were determined by immunoblot. The TdT-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptosis.


RESULTS
When SGC-7901 cells was treated with AG1478 or celecoxib alone, cell growth was only inhibited by high concentration of the two agents (10, 100 micromol/L) significantly, the IC50 of AG1478 and celecoxib were 69.69 micromol/L and 70.98 micromol/L respectively. Compared with AG1478 or celecoxib alone, combination of AG1478 and celecoxib at different doses significantly enhanced the inhibitive effects on cell growth (P < 0.01). Compared with control (56. 55%), the expression of PCNA was decreased in the cells treated with AG1478, celecoxib and the combination of these two agents, PCNA indeices were 26.24%, 38.16%, and 9.08%, respectively (P < 0.01). AG1478 induced cell apoptosis at 10 micromol/L, the rate was 7.88% vs. 3.54% in control (P < 0.01), and the combination of AG1478 with celecoxib showed an enhanced effect, the apoptosis rate was 14.90%. There were no any effects on ERK expression with the treatments of either AG1478, celecoxib alone or toghether, but the phospholation of ERK was decreased by AG1478 (P < 0.01).


CONCLUSIONS
AG1478 combined with celecoxib results in enhanced inhibitive effect on the growth of SGC-7901, which may partly due to the suppression of ERK phospholation.
Li
Rong-Kun
RK
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Qiang
Ou
O
Liao
Juan
J
Wang
Chun-Hui
CH
D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011720:Pyrazoles / Q000494:pharmacology*; D011799:Quinazolines; D013274:Stomach Neoplasms / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology*; D020032:Tyrphostins / Q000494:pharmacology*
D018809:Proliferating Cell Nuclear Antigen; D011720:Pyrazoles; D011799:Quinazolines; D013449:Sulfonamides; D020032:Tyrphostins; C101044:RTKI cpd; D066246:ErbB Receptors; D048052:Mitogen-Activated Protein Kinase 3; D000068579:Celecoxib