Zhang X, Atala A, Godbey W T
Department of Chemical and Biomolecular Engineering, Laboratory for Gene Therapy and Cellular Engineering, Lindy Boggs Center, Tulane University, New Orleans, LA 70118, USA.
Cancer Gene Ther. 2008 Aug;15(8):543-52. doi: 10.1038/cgt.2008.7. Epub 2008 Mar 7.
Targeted gene delivery for induced apoptosis of transitional cell carcinomas was carried out in vivo in mice via utilization of the murine cyclooxygenase type 2 (Cox-2) promoter (Tis10). MB49 cells, which constitutively overexpress Cox-2 like numerous other carcinomas, selectively expressed delivered genes that utilized this transcriptional control element. The products of the delivered genes were artificially inducible forms of caspases 3 and 9, which remained inactive until a chemical inducer of dimerization was later injected intraperitoneally. The genes were delivered intravesically as plasmids complexed with poly(ethylenimine). Significant improvements, in the form of reduced bladder mass, reduced tumor volume, anti-angiogenesis and inhibition of tumor growth were seen versus untreated or unactivated controls. In some instances, tumors were seen to go into complete remission. There were no apparent bystander effects associated with the treatments. This targeted gene therapy regimen could have wide applicability to numerous cancers due to constitutive overexpression of Cox-2.
通过利用小鼠环氧化酶2型（Cox-2）启动子（Tis10），在小鼠体内对移行细胞癌进行靶向基因递送以诱导细胞凋亡。MB49细胞像许多其他癌症一样组成性过表达Cox-2，选择性地表达利用这种转录控制元件的递送基因。递送基因的产物是半胱天冬酶3和9的人工可诱导形式，在后来腹腔注射二聚化化学诱导剂之前一直保持无活性。基因以与聚乙烯亚胺复合的质粒形式经膀胱内递送。与未治疗或未激活的对照相比，观察到膀胱质量减轻、肿瘤体积减小、抗血管生成和肿瘤生长抑制等显著改善。在某些情况下，肿瘤完全缓解。治疗未观察到明显的旁观者效应。由于Cox-2的组成性过表达，这种靶向基因治疗方案可能广泛适用于多种癌症。
