PNAS:揭秘炭疽霉素如何治疗癌症

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最近，来自美国国家过敏症和传染病研究所等机构的科学家通过研究揭示了，将炭疽毒素蛋白同当前化疗药物相结合帮助消除癌变的肿瘤组织，相关研究发表在了国际杂志PNAS上。

炭疽杆菌可以引发致死性的炭疽热，这种细菌会产生一种由三种蛋白组成的特殊毒素，而每一种蛋白却是非毒性的，因为这种蛋白可以被工程化修饰用来抑制肿瘤的生长，因此其或许就可以帮助开发新型的癌症疗法；然而截止到目前为止，科学家们并不确定炭疽毒素蛋白控制肿瘤生长的分子机制。

本文中，研究人员利用小鼠模型进行研究，结果发现，炭疽毒素蛋白可以通过特异性地靶向作用血管内壁细胞来发挥作用，而组织血管可以给肿瘤提供营养物质。这种蛋白可以通过CMG2细胞表面受体到达肿瘤细胞表面，抑制肿瘤细胞再生，由于这种毒素并不能靶向作用肿瘤自身，而仅能靶向作用宿主机体衍生的肿瘤血管细胞，因此其或可用作开发治疗一系列肿瘤的新型疗法。

但不幸的是，机体免疫系统会产生抗体来对炭疽毒素蛋白产生反应，从而使得疗法无效，为了克服这个困境，研究者对小鼠进行试验来检测是否化疗药物喷司他丁和环磷酰胺（PC）可以阻断机体产生可以中和炭疽毒素蛋白的特殊抗体；文章中研究者给小鼠接种肿瘤并且利用如下体系对小鼠进行治疗，这种体系包括：盐水对照组、炭疽毒素蛋白组、PC组或炭疽毒素蛋白结合PC组。4个循环的疗法后（42天），所有接受组合性疗法的小鼠都活了下来，而其它治疗组的小鼠则因为机体肿瘤生长不得到接受安乐死。此外研究者在接受组合疗法的小鼠中并没有检测到任何中和性抗体，甚至在四轮疗法后也是如此。这项研究结果表明，将炭疽毒素蛋白同PC疗法进行结合或许可以产生持久的抗肿瘤效应，这就为后期开发治疗癌症的新型靶向疗法提供了新的思路。（生物谷Bioon.com）

Scientists decode how anthrax toxin proteins might help treat cancerous tumors

Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Dental and Craniofacial Research (NIDCR), and the National Heart, Lung and Blood Institute (NHLBI), all parts of the National Institutes of Health (NIH), describe how combining engineered anthrax toxin proteins and existing chemotherapy drugs could potentially yield a therapy to reduce or eliminate cancerous tumors. The findings, based on testing in mice, will appear this week in the Early Edition of the Proceedings of the National Academy of Sciences.

The bacterium Bacillus anthracis, which causes the deadly anthrax disease, produces a toxin made of three proteins that individually are non-toxic. Because the proteins can be engineered to suppress tumor growth they have emerged as a potential cancer therapy. Until now, however, scientists have been unsure how the anthrax toxin proteins control tumor growth.

In this study, NIH scientists used mouse models to show that anthrax toxin proteins work by specifically targeting the cells that line the inner walls of the blood vessels feeding the tumor. The proteins, which reach these cells through a surface receptor called CMG2, prevent the cells from reproducing. Because the toxin does not target the tumor cells themselves but rather the host-derived blood vessel cells, the strategy could be efficacious for a wide range of tumor types, the NIH team notes.

Unfortunately, the immune system produces antibodies in response to the anthrax toxin proteins, making additional courses of treatment ineffective. To circumvent this problem, the investigators examined in mice whether a regimen of the chemotherapy drugs pentostatin and cyclophosphamide (PC) could block production of the antibodies that neutralize the anthrax toxin proteins. Mice were inoculated with tumors and treated with one of the following regimens: saline (for use as a placebo), anthrax toxin protein therapy, PC, or a combined regimen of anthrax toxin protein therapy and PC. After four cycles of therapy (42 days), all mice receiving the combined regimen were alive, whereas mice in the other groups had to be euthanized due to tumor growth. In addition, the investigators could not detect any neutralizing antibodies in the combined regimen group, even after the fourth round of therapy. Together, the results showed that the combined anthrax toxin protein and PC therapy has durable, anti-tumor effects worthy of further exploration, according to the authors.