[Inhibitory effects of celecoxib combined with octreotide on growth of multidrug resistant human gastric cancer cell line SGC7901/ADR].
OBJECTIVE
Both cyclooxygenase-2 (COX-2) inhibitor and octreotide can inhibit growth of tumor cells. This study was to investigate inhibitory effects of COX-2 inhibitor celecoxib alone, and celecoxib combined with octreotide on growth of multidrug resistant human gastric cancer cell line SGC7901/ADR.


METHODS
Experimental groups:(1)celecoxib (1 x 10(-4)-1 x 10(-8) mol/L); (2)octreotide (1 x 10(-5)-1 x 10(-9) mol/L); (3)celecoxib (1 x 10(-4)-1 x 10(-8) mol/L) combined with octreotide (1 x 10-6 mol/L);(4)control group (RPMI-1640 medium without serum). The effects of all treatments on SGC7901 cells, and SGC7901/ADR cells were observed. Cell proliferation was measured by (3)H-thymidine incorporation into DNA. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunocytochemistry. Cell apoptosis was measured by TdT-mediated dUTP nick end-labeling assay (TUNEL) and flow cytometry.


RESULTS
(3)H-thymidine incorporation into SGC7901/ADR cells treated with celecoxib [(471.3+/-79.7) cpm] was significantly lower than that of control group [(917.5+/-130.8) cpm](P< 0.05). When combined with octreotide, celecoxib presented lower (3)H-thymidine incorporation [(220.0+/-19.7)cpm] than it alone with a 53.3% decrease. The concentration of celecoxib in combination group negatively related to synthesis of DNA in SGC7901/ADR cells (r=0.996,P< 0.001). The expression of PCNA in either celecoxib group or combination group markedly decreased. The apoptosis rates of SGC7901/ADR cells induced by celecoxib alone, and combination treatment were 32.9%, and 52.5%.


CONCLUSIONS
Celecoxib combined with octreotide may enhance inhibition of growth of multidrug resistant human gastric cancer cells. The mechanism may be related with inhibiting DNA synthesis, and inducing apoptosis.
Zheng
Wen-Bin
WB
Division of Peptides Related with Human Diseases, Key Laboratory of Biotherapy of Human Diseases, Ministry of Education,West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Wang
Chun-Hui
CH
Qiang
Ou
O
Tang
Cheng-Wei
CW
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D015282:Octreotide / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D016861:Cyclooxygenase Inhibitors; D004273:DNA, Neoplasm; D018809:Proliferating Cell Nuclear Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D015282:Octreotide