Effects Of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Combined With Andrographolide On Human Renal Cell Carcinoma Cells

Renal cell carcinoma(RCC)accounts for 2% to 3% of adult malignancies,the number of new patients per year over 300,000.Surgery is the preferred treatment for RCC.However,for non-resectable and metastatic advanced renal cell carcinoma,effective treatment is limited,and toxic side effects.Tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)has a specific activity to induce tumor cell apoptosis by binding to death receptors(DR4 and DR5),and is not toxic to normal cells,which is a hot spot in anti-tumor research.However,TRAIL in addition to activation of the apoptotic signaling pathway,but also activate the cell non-apoptotic signaling pathways,leading to a variety of cancer cells in the production of TRAIL resistance.Our study confirmed that RCC cells are also resistant to TRAIL,TRAIL alone on the inhibition of RCC cells and poor killing effect.Interestingly,we found that the combination of andrographolide,which is approved by safety,is effective against RCC cell resistance.Compared with TRAIL or andrographolide alone,the combination of these two methods significantly enhanced the inhibitory effect on the cell viability,proliferation,cloning ability and migration of RCC cells,and induced cell cycle arrest and cell senescence of RCC cells in G2 phase RCC cell apoptosis and DNA damage.Subsequently,we used Caspase-8 and necrotic inhibitor to detect apoptosis-related protein and DNA damage marker ?-H2 AX by Western blot.It was found that the killing effect of TRAIL combined with andrographolide on RCC cells was mainly induced by Caspase-8 Dependent apoptosis and DNA damage.