根據芝加哥伊利諾州大學醫學院研究者研究發現,一種罕見的抗菌素有望成為抗癌劑,在大多數人類腫瘤中,有一個基因比在正常細胞中表達水平要高,而抗癌劑正是抑制該基因的表達。這項研究發表在《癌症研究》10月1日期刊上。
UIC醫學、微生物學和免疫學副教授Andrei Gartel作為該研究的主要研究者,他說,「我們選擇在癌細胞中過量表達的基因作為靶基因,通過研究有望發現抗癌劑。」
FoxM1基因是負責啟動細胞增殖的必須基因,同時負責關閉阻斷細胞增殖的基因。不受抑制的細胞增殖是癌細胞的一個特徵。
在天然螢光蛋白螢光素酶的基礎上,研究者發展了一種新的篩選系統,此系統可以用來鑑定抑制啟動和關閉基因蛋白的小分子。研究者用這個系統鑑定一種抗菌素:鹽層黴素A,它可以特異性地識別結合FoxM1而不影響其他細胞功能。
在進一步的組織培養實驗中,研究者發現,鹽層黴素A誘導癌細胞發生細胞凋亡,但不影響正常細胞的活性。
新的篩選方法為研究者提供了一條發現致癌基因因子的快捷途徑。Gartel認為,用此方法發現的第一個化合物是鹽層黴素A,鹽層黴素沒有毒性有望成為一種有效的抗癌劑。
在計劃實施人體試驗之前,鹽層黴素A必須首先在實驗室進行抑制其他細胞系的試驗和初步的動物實驗。
英文原文:
Antibiotic inhibits cancer gene activityA 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.