[Relationship between death receptor 5 and apoptosis in hepatocellular carcinoma].
OBJECTIVE
To investigate the antitumor efficacy of death receptor 5, its ligand (TRAIL) and DR5mAb in human hepatocellular carcinoma.


METHODS
Expression of DR5 in the HCC cell lines HepG2, SMMC 7721 and normal human liver cell line LO2 was measured at mRNA and protein level by semi-quantitative RT-PCR and Western blot, respectively. MTT method was used to measure the cell viability and flow cytometry assay was used to detect apoptosis so as to observe the inhibitory effect of TRAIL and DR5mAb on HCC cells.


RESULTS
Death receptor 5 was highly expressed in the HCC cell lines, but rarely expressed in normal human liver cell line (P < 0.01). With the increase of TRAIL concentration, the cell viability of HCC cells decreased gradually. However, when the concentration of TRAIL was above 1000 ng/ml, HCC cells were resistant to TRAIL, but still sensitive to DR5mAb. After incubation with DR5mAb (1000 ng/ml) for 24 h, the rate of apoptosis in HCC cells reached to 52.45% +/- 0.57%, which was higher than that incubated with TRAIL under the same condition (14.74% +/- 0.48%) (P < 0.05). The cell viability of normal human liver cell line treated with TRAIL tended to decline with the increase of the concentration, which was significantly different from that of matched control group. But DR5mAb had little effect on normal human liver cell line.


CONCLUSIONS
Death receptor 5 as a target plays an important role in the course of HCC apoptosis induction. Agonistic monoclonal antibody specific for human DR5 can selectively and effectively kill hepatocellular carcinoma cells in vitro, while is not harmful to normal human hepatocytes. It reveals that DR5mAb might provide a new direction in hepatocellular carcinoma treatment research.
Zhu
Ran-xu
RX
Institute of Liver Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Lin
Ju-sheng
JS
Song
Yu-hu
YH
Li
Pei-yuan
PY
Tao
Lu-wei
LW
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand