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研究发现抗菌素能抑制癌基因活性
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根据芝加哥伊利诺州大学医学院研究者研究发现，一种罕见的抗菌素有望成为抗癌剂，在大多数人类肿瘤中，有一个基因比在正常细胞中表达水平要高，而抗癌剂正是抑制该基因的表达。这项研究发表在《癌症研究》10月1日期刊上。 UIC医学、微生物学和免疫学副教授Andrei Gartel作为该研究的主要研究者，他说，“我们选择在癌细胞中过量表达的基因作为靶基因，通过研究有望发现抗癌剂。” FoxM1基因是负责启动细胞增殖的必须基因，同时负责关闭阻断细胞增殖的基因。不受抑制的细胞增殖是癌细胞的一个特征。 在天然荧光蛋白荧光素酶的基础上，研究者发展了一种新的筛选系统，此系统可以用来鉴定抑制启动和关闭基因蛋白的小分子。研究者用这个系统鉴定一种抗菌素：盐层霉素A，它可以特异性地识别结合FoxM1而不影响其他细胞功能。 在进一步的组织培养实验中，研究者发现，盐层霉素A诱导癌细胞发生细胞凋亡，但不影响正常细胞的活性。 新的筛选方法为研究者提供了一条发现致癌基因因子的快捷途径。Gartel认为，用此方法发现的第一个化合物是盐层霉素A，盐层霉素没有毒性有望成为一种有效的抗癌剂。 在计划实施人体试验之前，盐层霉素A必须首先在实验室进行抑制其他细胞系的试验和初步的动物实验。 英文原文： Antibiotic inhibits cancer gene activity A little-known antibiotic shows early promise as an anti-cancer agent, inhibiting a gene found at higher-than-normal levels in most human tumors, according to researchers at the University of Illinois at Chicago College of Medicine. Their findings appear in the Oct. 1 issue of Cancer Research. "We chose to target a gene believed to be over-expressed in cancer cells to screen for promising anti-cancer agents," said Andrei Gartel, assistant professor of medicine and of microbiology and immunology at UIC and principal investigator on the study. The FoxM1 gene is responsible for turning on genes needed for cell proliferation and turning off genes that block proliferation. Uncontrolled proliferation is characteristic of cancer cells. The researchers developed a new screening system, based on a naturally fluorescent protein called luciferase, to identify small molecules that inhibit proteins that turn genes on and off. Using this system, they identified an antibiotic, siomycin A, that specifically targets FoxM1 without affecting other cell functions. In further experiments in tissue cultures, the researchers found that siomycin A induced cancer cells, but not normal cells, to commit suicide in a process called apoptosis. The new screening technique, Gartel said, gives researchers a rapid way to find agents that target oncogenes -- genes believed to cause cancer. He said siomycin A, the first compound found with the method, "is particularly promising because we know that it is not toxic." Siomycin A must now be tested against other cell lines in the laboratory and in preliminary animal experiments before human trials could be planned. Only a tiny fraction of promising candidate drugs enter clinical trials, and few of those are ever approved. Gartel said the participation of the late Robert Costa, professor of biochemistry and molecular genetics at UIC and a leader in research on FoxM1, was critical for the success of the project thus far. Senthil Radhakrishnan, a visiting bioinformatics expert at UIC, is first author of the paper. Uppoor Bhat, Douglas Hughes and I-Ching Wang also contributed to the study. 来源：教育部科技发展中心 |
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2楼2006-10-22 16:59:18