Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells
Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells
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DOI：
10.1038/sj.onc.1205926
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发表时间：
2002-11-14
期刊：
影响因子：
8
通讯作者：
Fang, BL
中科院分区：
文献类型：
--
作者：
Lin, TY;Huang, XF;Fang, BL
我们评估了表达GFP/TRAIL融合基因的腺病毒载体（命名为Ad/gTRAIL）对人乳腺癌细胞株和正常人乳腺细胞的抗肿瘤活性和毒性作用。用Ad/gTRAIL治疗引起多种乳腺癌细胞系中高水平的转基因表达和凋亡。此外，用Ad/gTRAIL治疗有效地杀死对阿霉素或可溶性TRAIL蛋白耐药的乳腺癌细胞系。与此相反，只有最小的转基因表达和毒性检测后，正常人原发性乳腺上皮细胞用这种载体。体内研究进一步表明，Ad/gTRAIL的病灶内施用有效地抑制了源自多柔比星敏感性和多柔比星抗性乳腺癌细胞系的人肿瘤异种移植物的生长。具体而言，约50%的携带阿霉素敏感性和阿霉素耐药性乳腺癌异种移植物的动物显示出完全的肿瘤消退，并且保持无肿瘤超过5个月。这些结果表明，腺病毒编码的GFP/TRAIL基因的hTERT启动子驱动下，在癌症治疗中有潜在的应用。
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 tines 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.