Background: Cell-based gene therapy is considered as a promising strategy for the treatment of human malignancy. In many different types of cancer, mesenchymal stem cells (MSCs) are observed as valuable and potential anti-cancer agents. However, the exact mechanisms of MSCs involved in tumor microenvironment are not well understood.
Aim: Our aims are to elucidate the MSCs-mediated tumor microenvironment.
Materials and methods: In this study, colon cancer model was established by injecting the HT29 cells into the subcutaneous of right axilla of nude mice. We applied the human placenta-derived MSCs (hP-MSCs) armed with a double fusion gene containing the herpes simplex virus truncated thymidine kinase and firefly luciferase for treatment of colon cancer on days 10, 15, and 20 after HT29 cells injection. Molecular imaging methods were used for real-time imaging tumor progression and tracking transplanted hP-MSCs by bioluminescence imaging. Furthermore, proliferation and apoptosis-related proteins levels in colon cancer tissues were examined by immunofluorescence and Western blotting.
Results: Our results demonstrated that the administration of engineered hP-MSCs significantly inhibited the tumors and this effect was enhanced by ganciclovir application. Further analysis demonstrated the anti-tumor effect of engineered hP-MSCs in vivo depended on inhibiting tumor proliferation and inducing tumor apoptosis.
Conclusion: Collectively, this work showed that engineered hP-MSCs could inhibit colon cancer progression and metastasis by inducing tumor cell death and suppressing proliferation.
Keywords: tumor microenvironment, mesenchymal stem cells, malignant tumor, gene therapy, bioluminescence imaging