Effects of non-cytotoxic drugs on the growth of multidrug-resistance human gastric carcinoma cell line.
OBJECTIVE
To investigate the effects of the non-cytotoxic drug (cyclooxygenase-2 (COX-2) inhibitor and octreotide) on growth of the multidrug-resistant human gastric carcinoma cell line SGC-7901/ADR.


METHODS
The effects of non-cytotoxic drug on the growth of SGC-7901 and SGC-7901/ADR cells were evaluated by (3)H-thymidine incorporation assay. The apoptosis of cells was measured by the TdT-mediated dUTP nick end-labeling assay (TUNEL) and flow cytometric assay. Western blotting was used to analysis the expression of cyclooxygenase (COX-2) protein in SGC-7901 cells and SGC-7901/ADR cells and P-glycoprotein (P-gp) from SGC-7901/ADR cells with variable treatments. Activator protein-1 binding activity was examined by electrophoretic mobility shift assay.


RESULTS
(3)H-thymidine incorporation into SGC-7901/ADR cells treated with celecoxib was significantly lower than that of control group (471.3 +/- 79.7 cpm vs 917.5 +/- 130.8 cpm, P < 0.05). When combined with octreotide, celecoxib presented lower (3)H-thymidine incorporations than its used alone and decreased to 53.3% of that amount original. Either celecoxib or the combination group markedly induced apoptosis in SGC-7901/ADR cells. COX-2 protein in the SGC-7901/ADR cells was higher than in that of the SGC-7901 cells (1.543 +/- 0.052 vs 0.564 +/- 0.021, P < 0.05). The inhibition of P-gp could be achieved with celecoxib alone and combination with octreotide (0.486 +/- 0.012, 0.252 +/- 0.014 vs 0.941 +/- 0.033, P < 0.05). Moreover, AP-1 binding activity could be suppressed by non-cytotoxic drug and showed a synergistic effect.


CONCLUSIONS
The combination of non-cytotoxic drug significantly improved the inhibitive effects on the growth of multidrug-resistant human gastric cancer cells.
Wang
Chun Hui
CH
Department of Gastroenterology, West China Hospital, Sichuan University, Sichuan Province, China.
Zheng
Wen Bin
WB
Qiang
Ou
O
Tang
Cheng Wei
CW
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000032:analysis; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018809:Proliferating Cell Nuclear Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D018808:Transcription Factor AP-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib; D015282:Octreotide