Neoplasma. 2013;60(6):613-9. doi: 10.4149/neo_2013_079.
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.
癌症放射治疗研究中的一个关键问题是使肿瘤细胞对电离辐射的细胞杀伤作用敏感，同时使正常组织保持完整。实现这一目标的一种潜在方法是基因放射治疗，即放射治疗和基因治疗的结合。选择某些外源性辐射诱导的调节基因，例如早期生长反应-1（Egr-1），并在电离辐射下转录其下游肿瘤治疗基因，以便在转染和照射暴露后通过表达的基因产物协同杀死肿瘤细胞。在这项研究中，我们构建了一个在辐射诱导的 Egr-1 启动子控制下同时编码 TRAIL 和内皮抑素的质粒，并评估了其与放射治疗联合的抗肿瘤疗效。我们的质粒在转染乳腺癌细胞并接受 X 射线照射后，显著上调了 TRAIL 和内皮抑素蛋白的水平。体外检测到的细胞效应表明，基于 TRAIL-内皮抑素的基因治疗可以通过抑制肿瘤细胞生长、促进细胞凋亡和诱导细胞周期停滞来增强乳腺癌细胞的放射增敏作用。总之，我们的研究结果表明，TRAIL-内皮抑素靶向方法可能是一种有前途的方法，可以使实体肿瘤对放射治疗敏感。
