含尿激酶受体靶向融合蛋白 L-甲硫氨酸酶选择性抑制癌细胞生长。
Selective growth inhibition of cancer cells by L-methioninase-containing fusion protein targeted to the urokinase receptor.
机构信息
Bioengineering Center and School of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman, Oklahoma 73117, USA.
出版信息
Pharmacology. 2009;84(5):271-5. doi: 10.1159/000242997. Epub 2009 Oct 1.
BACKGROUND
We have reported the development of a novel fusion protein (FP) consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase (L-M). The present study compared the effect of this novel FP on the proliferation of human ovarian, skin, breast endometrial and pancreatic cancer cell lines.
METHODS
The FP, L-M and a mutated FP, with reduced L-M activity, were produced by recombinant methods. The effect of treatment with FP, L-M and mutated FP on the proliferation of the cancer cells was measured in vitro using an MTS assay.
RESULTS
The inhibitory effect of the FP was found to be significantly greater than that of L-M alone or the mutated FP. In addition, the FP produced a greater inhibitory effect on an ovarian cancer cell line than on comparable normal, non-cancerous cells. Further, the FP produced a dose-dependent inhibition of the proliferation of pancreatic cancer cell lines.
CONCLUSION
These results suggest that this FP is a potent and selective inhibitor of the proliferation of various cancer cell lines and has potential as a therapeutic agent for the treatment of various methionine-dependent cancers.
背景
我们已经报道了一种新型融合蛋白（FP）的开发，该蛋白由尿激酶的氨基末端片段与酶 L-蛋氨酸酶（L-M）的氨基末端连接而成。本研究比较了这种新型 FP 对人卵巢、皮肤、乳腺、子宫内膜和胰腺癌细胞系增殖的影响。
方法
通过重组方法生产 FP、L-M 和活性降低的突变 FP。使用 MTS 测定法在体外测量 FP、L-M 和突变 FP 处理对癌细胞增殖的影响。
结果
FP 的抑制作用明显大于单独的 L-M 或突变 FP。此外，FP 对卵巢癌细胞系的抑制作用大于可比的正常非癌细胞系。此外，FP 对胰腺癌细胞系的增殖呈剂量依赖性抑制。
结论
这些结果表明，这种 FP 是一种有效且选择性的多种癌细胞系增殖抑制剂，具有作为治疗各种依赖蛋氨酸的癌症的治疗剂的潜力。
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