Fang Fang1, Ai-ping Wang, Shi-fang Yang. 1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Abstract
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 0.32-1 000 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 microg/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 resistant to rmh TRAIL. The results suggested that rmh TRAIL might be a useful anticancer agent in future.
AIM: To investigate the antitumor activity and safety of a novel recombinant mutant humantumornecrosis factor-related apoptosis-inducing ligand (rmhTRAIL). METHODS: Antitumor activity of rmhTRAIL was evaluated by using several tumor cell lines by MTT assay in vitro, and by using a mouse xenograft model in vivo. rmhTRAIL-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 rmhTRAIL was also evaluated in several normal human cell lines. RESULTS: At the concentration of 0.32-1 000 ng/mL, rmhTRAIL 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 microg/mL, rmhTRAIL showed no or mild cytotoxicity in the normal cell lines. rmhTRAIL (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 rmhTRAIL treatment. The percentage of apoptotic cells induced by rmhTRAIL in NCI-H460 cells was significantly higher than that by wt TRAIL. CONCLUSION:rmhTRAIL provided potent antitumor activity in vivo and in vitro, whereas most normal human cells were resistant to rmhTRAIL. The results suggested that rmhTRAIL might be a useful anticancer agent in future.
Authors: Adam Bilski; Grażyna Pasz-Walczak; Robert Kubiak; Piotr Sek; Justyna Chalubinska; Wojciech Fendler; Konrad Wronski; Anna Piekarska; Piotr Pluta; Piotr Potemski; Arkadiusz Jeziorski; Janusz Piekarski Journal: Arch Med Sci Date: 2010-09-07 Impact factor: 3.318