Lin Tongyu, Huang Xuefeng, Gu Jian, Zhang Lidong, Roth Jack A, Xiong Momiao, Curley Steven A, Yu Yinhua, Hunt Kelly K, Fang Bingliang
Department of Thoracic and Cardiovascular Surgery, Section of Thoracic Molecular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Oncogene. 2002 Nov 14;21(52):8020-8. doi: 10.1038/sj.onc.1205926.
We evaluated anti-tumor activity and toxic effect of an adenoviral vector expressing the GFP/TRAIL fusion gene from the hTERT promoter (designated Ad/gTRAIL) on human breast cancer cell lines and on normal human breast cells. Treatment with Ad/gTRAIL elicited high levels of transgene expression and apoptosis in a variety of breast cancer cell lines. Furthermore, treatment with Ad/gTRAIL was effective in killing breast cancer lines resistant to doxorubicin or soluble TRAIL protein. In contrast, only minimal transgene expression and toxicity was detected in normal human primary mammary epithelial cells after treatment with this vector. An in vivo study further showed that the intralesional administration of Ad/gTRAIL effectively suppressed the growth of human tumor xenografts derived from both doxorubicin-sensitive and doxorubicin-resistant breast cancer lines. Specifically, about 50% of animals bearing doxorubicin-sensitive and doxorubicin-resistant breast cancer xenografts showed complete tumor regression and remained tumor-free for over 5 months. These results suggest that the adenovirus encoding the GFP/TRAIL gene driven by the hTERT promoter has potential application in cancer therapy.
我们评估了一种从人端粒酶逆转录酶（hTERT）启动子表达绿色荧光蛋白/肿瘤坏死因子相关凋亡诱导配体（GFP/TRAIL）融合基因的腺病毒载体（命名为Ad/gTRAIL）对人乳腺癌细胞系和正常人乳腺细胞的抗肿瘤活性及毒性作用。用Ad/gTRAIL处理可在多种乳腺癌细胞系中引发高水平的转基因表达和细胞凋亡。此外，用Ad/gTRAIL处理对阿霉素或可溶性TRAIL蛋白耐药的乳腺癌细胞系有效。相比之下，用该载体处理后，在正常人原代乳腺上皮细胞中仅检测到最低限度的转基因表达和毒性。一项体内研究进一步表明，瘤内注射Ad/gTRAIL可有效抑制源自阿霉素敏感和阿霉素耐药乳腺癌细胞系的人肿瘤异种移植物的生长。具体而言，约50%携带阿霉素敏感和阿霉素耐药乳腺癌异种移植物的动物显示肿瘤完全消退，并在超过5个月内无肿瘤。这些结果表明，由hTERT启动子驱动的编码GFP/TRAIL基因的腺病毒在癌症治疗中具有潜在应用价值。
