The Anti-tumor Effect Of Human Umbilical Cord Mesenchymal Stem Cells Delivering STRAIL In Lung Cancer

Objective: This study aimed to explore the role of MCP-1/CCR2 axis in human umbilical cord mesenchymal stem cells(HUMSCs) homing to lung cancer and the anti-tumor effects of its delivering s TRAIL.Methods: Subcutaneous lung cancer xenograft model was established in BALB/c nude mice. Bioluminescence imaging(BLI) and transwell migration assay were used to monitor the tropism of HUMSCs to lung cancer in vivo and in vitro. ELISA was utilized to detect the secretion of monocyte chemoatrractant protein-1(MCP-1) in lung cancer cell culture supernatant. Flow cytometry was applied to investigate the expression of MCP-1 receptor CCR2 on HUMSCs. After knocking down the MCP-1 expression in lung cancer cells by infecting sh RNA or blocking CCR2 on HUMSCs by inhibitor RS504393, the migration ability of HUMSCs was determined by transwell assay in vitro. HUMSCs were transduced with lentivirus packaged in 293 T cells to stably express s TRAIL(MSC.ISZ-s TRAIL) and were injected intravenously into tumor-bearing mice. Tumor volume was measured every 3 days. On day 22 after treatment, tumors and blood were harvested. Hematoxylin and eosin(H&E) staining and terminal deoxynucleotidyl transferase d UTP nick-end labeling(TUNEL) staining were used to assess the anti-tumor effects of treatment. Spectrophotometer was utilized to detect the serum level of alanine aminotransferase(ALT) and aspartate transaminase(AST) to assess the safety.Results: Subcutaneous lung cancer xenograft model was successfully established. HUMSCs migrated to lung cancer in vivo and in vitro. Lung cancer cells and HUMSCs highly expressed MCP-1 and CCR2 respectively. Both silencing MCP-1 in A549 cells and inhibiting CCR2 on HUMSCs resulted in the significant decrease of HUMSCs migration. MSC.ISZ-s TRAIL induced tumor necrosis and intensively lung cancer cell apoptosis in therapuetic model, and no obvious change of ALT and AST level was found among all groups.Conclusion: Our study originally indicated MCP-1/CCR2 axis promoted the migration of HUMSCs to lung cancer, and confirmed the anti-tumor potential of MSC.ISZ-s TRAIL. These results will motive the clinical application of MSC-based cancer therapy in future.