[Antitumor effects of specific cyclooxygenase inhibitors combined with chemotherapeutic agents on gastric cancer cells in vitro].
OBJECTIVE
To study the effects of two specific cyclooxygenase inhibitors (SCI), rofecoxib and celecoxib, combined with chemotherapeutic drugs 5-Fu, DDP and VP-16 on gastric cancer cell line BGC-823, and to evaluate whether specific cyclooxygenase inhibitors can be used as a synergetic agent in chemotherapy.


METHODS
The gastric cancer cell line BGC-823 cells were incubated for 48 hours with rofecoxib and celecoxib, 5-Fu, DDP and VP-16 (concentration gradient of 5-Fu, DDP and VP-16:1 microg/ml, 10 microg/ml and 100 microg/ml), or in combination, respectively. MTT working solution was added to each culture and calculated the survival rates of gastric cancer cells. Median-effect principle and Professor Jin's evaluation methods were applied to detect the interaction between the specific cyclooxygenase inhibitors and chemotherapeutic agents.


RESULTS
The inhibition rates of gastric cancer cells were 42.63% +/- 1.26% and 50.67% +/- 2.35% by treatment with 0.1 micromol/L rofecoxib and 50 micromol/L celecoxib, respectively. The inhibition rates of gastric cancer cells by treatment with 5-Fu, DDP and VP-16 at different concentrations (1 microg/ml, 10 microg/ml and 100 microg/ml) were 39.75% +/- 3.14%, 49.96% +/- 2.08%, 87.93% +/- 3.66%; 48.28% +/- 2.08%, 59.46% +/- 1.69%, 88.23% +/- 4.81%; and 29.23% +/- 3.27%, 49.34% +/- 3.75%, 79.24% +/- 2.44%, respectively. However, the inhibition rates showed a synergetic role while combined the two SCI (0.1 micromol/L rofecoxib and 50 micromol/L celecoxib) with chemotherapeutic agent at different concentrations (P <0.05).


CONCLUSIONS
Both rofecoxib and celecoxib have an ability to suppress gastric cancer cells in vitro, and the synergetic role becomes evident when rofecoxib and celecoxib are combined with chemotherapeutic agents at different concentrations, which indicate that the two specific cyclooxygenase inhibitors may be used as a chemotherapeutic sensitizer.
Zhu
Feng-shang
FS
Department of Gastroenterology, Tongji Hospital of Tongji University, Shanghai, China. fszhudoc@sina.com
Chen
Xi-mei
XM
Wang
Yi-jun
YJ
Zhang
Xia
X
Feng
Jiu-xian
JX
D000230:Adenocarcinoma / Q000473:pathology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D005047:Etoposide; D000068579:Celecoxib; D002945:Cisplatin; D005472:Fluorouracil