[Synergistic lethal effect of mDRA-6 and nimesulide on human hepatocellular cancer cell line SMMC-7721].
OBJECTIVE
Both mDRA-6, a monoclonal antibody of death receptor 5 (DR5) in human cells prepared by our key laboratory, and nimesulide, a specific cyclooxygenase-2 (COX-2) inhibitor, can induce apoptosis of some malignant tumor cells. This study was to investigate the lethal effects of mDRA-6 and nimesulide on human hepatocellular cancer cell line SMMC-7721, and explore the possible mechanism.


METHODS
The expression of DR5 on SMMC-7721 cells was detected by flow cytometry (FCM). SMMC-7721 cells were treated with mDRA-6 and nimesulide alone or in combination. Cell morphology was observed under microscope with Hoechst33258 staining. Cytotoxicity was examined by MTT assay. Cell apoptosis was detected by FCM.


RESULTS
The positive rate of DR5 on SMMC-7721 cells was 95.0%. The apoptosis of SMMC-7721 cells could be induced by both mDRA-6 and nimesulide: the apoptosis rates were 10.5% when treated with 25 ng/mL mDRA-6 for 12 h, 35.0% when treated with 1 600 ng/mL mDRA-6, 5.0% when treated with 200 micromol/L nimesulide, and 34.0% when treated with 800 micromol/L nimesulide. The combination of mDRA-6 and nimesulide exhibited synergistic effect on the apoptosis of SMMC-7721 cells (q=1.23): the apoptosis rates were 31.2% when treated with 200 micromol/L nimesulide and 25 ng/mL mDRA-6 for 12 h, and 91.1% when treated with 200 micromol/L nimesulide and 1 600 ng/mL mDRA-6 for 12 h.


CONCLUSIONS
Both mDRA-6 and nimesulide can induce the apoptosis of SMMC-7721 cells. The combination of mDRA-6 and nimesulide exhibits synergistic lethal effect on SMMC-7721 cells.
Liu
Ying-Jie
YJ
Institute of Immunology, Key Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan, 475004, PR China.
Ma
Yuan-Fang
YF
Zhang
Jun
J
Zhao
Yue-Ping
YP
Bai
Hui-Ling
HL
Li
Shu-Lian
SL
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000502:physiology; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis / Q000276:immunology*; D013449:Sulfonamides / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C012655:nimesulide