Radiosensitization of breast cancer cells by TRAIL-endostatin-targeting gene therapy

Abstract

One of the key issues in cancer radiotherapy research is to sensitize tumor cells to the cell killing effects of ionizing radiation while leaving normal tissues intact. One potential approach to achieve this is gene-radiotherapy, i.e. a combination of radiation therapy and gene therapy. It is to choose certain exogenous radiation-inducible regulatory genes, for example, early growth response-1 (Egr-1), and transcript its downstream tumor-therapeutic genes under ionizing radiation so as to kill the tumor cells synergistically by the expressed gene products together after transfection and irradiation exposure. In this study, we engineered a plasmid encoding both TRAIL and endostatin under the control of the radiation-inducible Egr-1 promoter, and evaluated its anti-tumor efficacy in combination with radiotherapy. Our plasmid showed significant efficacy in up-regulating the levels of TRAIL and endostatin proteins after transfected into breast cancer cells and exposed to X-ray irradiation. The detected cellular effects in vitro manifested that TRAIL-endostatin-based gene therapy could enhance radiosensitizing effects in breast cancer cells in terms of tumor cell growth inhibition, promoting apoptosis and the induction of cell cycle arrest. In summary, our results suggest that TRAIL-endostain-targeting approach might be a promising method to sensitize solid tumors to radiation therapy.