Department of Thoracic Surgery, Qilu Hospital, Shandong University, Jinan 250012, China
Department of Orthopedics, Shandong Province Hospital, Shandong University, Jinan 250021, China.
Acta Biochim Biophys Sin (Shanghai). 2014 Jun;46(6):471-6. doi: 10.1093/abbs/gmu024. Epub 2014 Apr 15.
The apoptotic ligand TNF-related apoptosis-inducing ligand (TRAIL) is believed to be a promising candidate for cancer gene therapy, yet gene therapy strategies to tackle this disease systemically are often impaired by inefficient delivery of the vector to the tumor tissue. Mesenchymal stem cells (MSCs) have been shown to home to tumor sites and could potentially act as a shield and vehicle for an antitumor gene therapy vector. Here, we used an adenoviral vector expressing TRAIL to transduce MSCs and studied the apoptosis-inducing activity of these TRAIL-carrying MSCs on esophageal cancer cell Eca-109. Our results showed that, in vitro, TRAIL-expressing MSCs were able to inhibit proliferation and induce apoptosis in Eca-109 cells by an MTT assay, co-culture experiments and flow cytometry analysis. In vivo, TRAIL-expressing MSCs also displayed an ability to inhibit tumor growth in an Eca-109 xenograft mouse model. Together, our findings indicated that the gene therapy strategy of MSCs-based TRAIL gene delivery has a wide potential value for improving the treatment of esophageal cancer.
凋亡配体 TNF 相关凋亡诱导配体（TRAIL）被认为是癌症基因治疗的有前途的候选物，但针对这种疾病的全身性基因治疗策略通常因载体向肿瘤组织的有效传递而受到阻碍。间充质干细胞（MSCs）已被证明可以归巢到肿瘤部位，并且可以作为抗肿瘤基因治疗载体的盾牌和载体。在这里，我们使用表达 TRAIL 的腺病毒载体转导 MSCs，并研究了这些携带 TRAIL 的 MSC 对食管癌细胞 Eca-109 的凋亡诱导活性。我们的结果表明，在体外，通过 MTT 测定、共培养实验和流式细胞术分析，表达 TRAIL 的 MSC 能够抑制 Eca-109 细胞的增殖并诱导其凋亡。在体内，表达 TRAIL 的 MSC 也显示出抑制 Eca-109 异种移植小鼠模型中肿瘤生长的能力。总之，我们的研究结果表明，基于 MSC 的 TRAIL 基因传递的基因治疗策略具有广泛的潜在价值，可以改善食管癌的治疗效果。
