Apoptosis Of Osteosarcoma Cell MG-63 Effectively Induced By A Combination Of TRAIL And Low Does Of THP

ObjectiveTumor necrosis factor-related apoptosis inducing ligand(TRAIL)is a member of tumor necrosis factor(TNF)family.It has a selective cytotoxicity of tumor cells while had no significant side effects to normal cells.So it has a good prospect for clinical application in cancer treatment.However,some tumor cells is not sensitive or tolerant to TRAIL-induced apoptosis,so how to improve anti-tumor activity of TRAIL and how to overcome TRAIL resistance has become a hot research.In this study,we observe whether there is a synergistic induction of human osteosarcoma MG-63 cell apoptosis,with TRAIL and chemotherapy drug THP combination together,and to explore the molecular mechanisms which may exist,providing the theoretical basis for the clinical application of TRAIL.MethodsDifferent concentrations of TRAIL was used alone or in combination with THP on conventional cultured cell line MG-63,cell inhibition rate was evaluated by MTT after 24 hours, the morphological changes of cells observed under the inverted microscope ,the proportion of apoptosis detected by flow cytometry assay,the related gene expression levels detected by RT-PCR.Results1.TRAIL and THP can inhibit the proliferation of MG-63 cells,MG-63 cell is not sensitive to TRAIL,IC50>10μg/ml,but relatively sensitive to THP,IC50<10μg/ml2.Subtoxic concentration of THP combined with different concentrations of TRAIL showed a high synergy(P<0.05),all cofactors were more than 1.3.Observation under the inverted microscope and detection by flow cytometry assay confirmed that synergistic killing effect achieved mainly through the induction of apoptosis.4.RT-PCR showed death receptors DR4 and DR5 expression levels were significantlyhigher after drug used.ConclusionTRAIL can effectively induce human osteosarcoma cells MG-63 apoptosis in combination of subtoxic does of THP,the change of death receptors DR4 and DR5 expession levels before and after drug used may be involved in apoptosis.