Worth L L, Jia S F, Zhou Z, Chen L, Kleinerman E S
Department of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Clin Cancer Res. 2000 Sep;6(9):3713-8.
The purpose of these studies was to determine the effect of adenovirus-mediated interleukin-12 (IL-12) gene transfer on the growth and development of osteosarcoma (OS) lung metastases in nude mice. A nude mouse model was produced by repetitive cycling of human SAOS OS cells through the lung. The resultant SAOS-LM6 cell line produced microscopic lung metastases by 5-6 weeks after i.v. injection of the tumor cells, with visible lung metastases present 8 weeks after injection. Transfection of SAOS-LM6 cells with a plasmid containing the murine IL-12 gene resulted in a decrease in metastatic potential. Animals injected with IL-12-transfected clones had fewer metastases compared with mice injected with SAOS-LM6 cells transfected with a control plasmid. Furthermore, nasal delivery of an adenoviral vector containing the murine IL-12 gene resulted in the inhibition of pulmonary metastases. Together, these data indicate that IL-12 may be an effective agent against OS and that nasal delivery may offer a unique way to deliver the gene to the local tumor environment, potentially decreasing systemic toxic effects.
这些研究的目的是确定腺病毒介导的白细胞介素-12（IL-12）基因转移对裸鼠骨肉瘤（OS）肺转移生长和发展的影响。通过将人SAOS骨肉瘤细胞反复循环通过肺部建立裸鼠模型。静脉注射肿瘤细胞后5至6周，所得的SAOS-LM6细胞系产生微小的肺转移灶，注射后8周出现可见的肺转移灶。用含有小鼠IL-12基因的质粒转染SAOS-LM6细胞导致转移潜能降低。与注射用对照质粒转染的SAOS-LM6细胞的小鼠相比，注射IL-12转染克隆的动物转移灶更少。此外，经鼻递送含有小鼠IL-12基因的腺病毒载体导致肺转移受到抑制。总之，这些数据表明IL-12可能是一种抗骨肉瘤的有效药物，经鼻递送可能提供一种将基因递送至局部肿瘤环境的独特方式，有可能降低全身毒性作用。
