Open AccessAntitumor activity of a novel recombinant mutant human tumor necrosis factor‐related apoptosis‐inducing ligand 1
Author(s) -
FANG Fang,
WANG Aiping,
YANG Shifang
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00206.x
Subject(s) - apoptosis , tunel assay , in vivo , biology , programmed cell death , tumor necrosis factor alpha , cell culture , flow cytometry , cancer research , mtt assay , in vitro , necrosis , cytotoxicity , microbiology and biotechnology , immunology , biochemistry , genetics
Aim: To investigate the antitumor activity and safety of a novel recombinant mutant human tumor necrosis factor‐related apoptosis‐inducing ligand (rmh TRAIL). Methods: Antitumor activity of rmh TRAIL was evaluated by using several tumor cell lines by MTT assay in vitro , and by using a mouse xenograft model in vivo . rmh TRAIL‐induced apoptosis in tumor cells was detected by cell death enzyme‐linked immunosorbent assay (ELISA), TdT‐mediated dUTP nick‐end labeling (TUNEL) assay and flow cytometry. The safety of rmh TRAIL was also evaluated in several normal human cell lines. Results: At the concentration of 0.32–1000 ng/mL, rmh TRAIL remarkably inhibited the proliferation of 5 tumor cell lines from lung, colon, and breast cancer compared with wild type (wt TRAIL) in vitro, whereas at the concentration of 1 ng/mL‐10 μg/mL, rmh TRAIL showed no or mild cytotoxicity in the normal cell lines. rmh TRAIL (3,15 mg/kg, ip, once daily for 10 d) exerted a significant inhibition on the growth of xenograft tumor NCI‐H460 in nude mice compared with the saline group ( P <0.01), and was more potent than wt TRAIL, a positive control. The apoptosis of NCI‐H460 cells was markedly induced in a concentration‐dependent and time‐dependent manner after rmh TRAIL treatment. The percentage of apoptotic cells induced by rmh TRAIL in NCI‐H460 cells was significantly higher than that by wt TRAIL. Conclusion: rmh TRAIL provided potent antitumor activity in vivo and in vitro, whereas most normal human cells were resisitant to rmh TRAIL. The results suggested that rmh TRAIL might be a useful anticancer agent in future.