[Treatment of osteosarcoma with TNF-related apoptosis-inducing ligand or in combination with doxorubicin in animal experiment].

OBJECTIVE: To examine the effect of TNF-related apoptosis-inducing ligand (TRAIL) and in combination with doxorubicin (ADM) to xenografted tumors in nude mice and to explore its potential mechanism. METHODS: MG-63 cells (5 x 10(6)/ml) were suspended in 0.2 ml RPMI-1640 and inoculated subcutaneously into the lower limb of nude mice. Treatment groups were given TRAIL of different concentration or combination of TRAIL and ADM intraperitoneally. Normal saline was administrated in the control group. Anti-tumor effects were estimated by tumor volumes. Serum alkaline phosphatase (ALP) was detected by ALP kits. Induction of apoptosis in xenografted tumors was confirmed by TUNEL (TdT-mediated dUTP nick end labeling) assay. Expression of Bax was detected by immunohistochemical assay. Expression of TRAIL receptors was detected by RT-PCR assay. RESULTS: Growth curve of tumors indicated that tumors carried by TRAIL-treated mice grew more slowly than that with normal saline and 2 microg TRAIL was more effective, Also tumors treated with combination of TRAIL and ADM grew more slowly than any other group. ALP activities of each group were moderately different but significance was not reached. TUNEL showed that there were more apoptotic cells in the combination group than any other group. Immunohistochemical assay showed that expression of Bax was up-regulated in the combination group. RT-PCR showed that expression of TRAIL-R2 mRNA was up-regulated in the combination group. CONCLUSION: TRAIL can induce an effective apoptosis of osteosarcoma cells in vivo in a dose-dependent fashion. ADM can enhance the effect of TRAIL-mediated apoptosis. And up-regulations of Bax and TRAIL-R2 may be the involved mechanism.