近日，美国罗切斯特大学的研究人员发现了盲鼹鼠对抗癌症的机制，这与三年前他们发现的裸鼹鼠对抗癌症的机制不同，相关论文发表在国际期刊《PNAS》杂志上。盲鼹鼠是中东地区常见的生活于地下的小型啮齿动物，其寿命可达21年。

　　盲鼹鼠和裸鼹鼠都是生活在地下的长寿啮齿动物，也是仅有的两种不会患癌症的哺乳动物。三年前，这个研究团队发现一个特殊的基因P16使得裸鼹鼠体内的癌细胞对过度拥挤异常敏感，即当细胞过度增殖生存环境变得拥挤时便停止生长。

　　Seluanov说，原本认为盲鼹鼠阻止癌细胞生长的机制与裸鼹鼠相同，但是二者却进化出各自的机制。盲鼹鼠体内异常生长的细胞可通过分泌interferon beta蛋白将自己快速杀死，Vera Gorbunova和Andrei Seluanov教授领导了此项研究，他们希望借以找到治疗癌症的方法。

　　研究者首先从盲鼹鼠体内分离出成纤维细胞，在体外进行培养，在分裂了大约15-20次之后，所有的细胞都迅速死亡了。这是因为细胞达到了癌症前期状态，分泌的自杀蛋白interferon beta不但杀死了癌细胞本身也杀死了其周围可能发展为癌细胞的细胞。

　　Gorbunova说，虽然人类没有像盲鼹鼠杀死癌细胞的机制，但是如果我们能够刺激癌症患者体内的癌细胞也产生如盲鼹鼠将癌细胞一网打尽的反应，那么攻克癌症将不是难题。他认为这种抗癌机制是盲鼹鼠对地下生活适应的结果，在进一步的研究中，研究者希望找到促进了interferon beta分泌的具体机制。

　　Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism

　　Vera Gorbunovaa,1, Christopher Hinea,2, Xiao Tiana, Julia Ablaevaa, Andrei V. Gudkovb, Eviatar Nevoc,1, and Andrei Seluanova

　　Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance to cancer. Spontaneous tumors have never been observed in spalacids. To understand the mechanisms responsible for this resistance, we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells proliferated actively for 7–20 population doublings, after which the cells began secreting IFN-β, and the cultures underwent massive necrotic cell death within 3 d. The necrotic cell death phenomenon was independent of culture conditions or telomere shortening. Interestingly, this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat, Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death. Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-β. Thus, we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground.

　　The team of researchers, led by Professor Vera Gorbunova and Assistant Professor Andrei Seluanov, found that abnormally growing cells in blind mole rats secrete the interferon beta protein, which causes those cells to rapidly die. Seluanov and Gorbunova hope the discovery will eventually help lead to new cancer therapies in humans. Their findings are being published this week in the Proceedings of the National Academy of Sciences.

　　Blind mole rats and naked mole rats—both subterranean rodents with long life spans—are the only mammals never known to develop cancer. Three years ago, Seluanov and Gorbunova determined the anti-cancer mechanism in the naked mole rat. Their research found that a specific gene—p16—makes the cancerous cells in naked mole rats hypersensitive to overcrowding, and stops them from proliferating when too many crowd together.

　　"We expected blind mole rats to have a similar mechanism for stopping the spread of cancerous cells," said Seluanov. "Instead, we discovered they've evolved their own mechanism."

　　Gorbunova and Seluanov made their discovery by isolating cells from blind mole rats and forcing them to proliferate in culture beyond what occurs in the animal. After dividing approximately 15-20 times, all of the cells in the culture dish died rapidly. The researchers determined that the rapid death occurred because the cells recognized their pre-cancerous state and began secreting a suicidal protein, called interferon beta. The precancerous cells died by a mechanism which kills both abnormal cells and their neighbors, resulting in a "clean sweep."

　　"Not only were the cancerous cells killed off, but so were the adjacent cells, which may also be prone to tumorous behavior," said Seluanov.

　　"While people don't use the same cancer-killing mechanism as blind mole rats, we may be able to combat some cancers and prolong life, if we could stimulate the same clean sweep reaction in cancerous human cells," said Gorbunova.

　　The research team also included Christopher Hine, Xiao Tian, and Julia Ablaeva in Rochester, Andrei Gudkov at Roswell Park Cancer Institute in Buffalo, NY, and Eviatar Nevo at the University of Haifa in Israel.

　　Gorbunova and Seluanov say they next want to find out exactly what triggers the secretion of interferon beta after cancerous cells begin proliferating in blind mole rats.

　　Gorbunova believes the anti-cancer mechanism is an adaptation to subterranean life. "Blind mole rats spend their lives in underground burrows protected from predators," said Gorbunova. "Living in this environment, they could perhaps afford to evolve a long lifespan, which includes developing efficient anti-cancer defenses."