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TEXT 94

Cancer biology

肿瘤生物学

Cramping tumours

断了肿瘤的活路（陈继龙编译）

Jan 18th 2007

From The Economist print edition

 

An old observation about cancer cells may lead to a new treatment

早年发现的肿瘤细胞的一个特征可能为治疗肿瘤打开新路子

 

CANCER cells manage their energy production in a most peculiar way.（1）A healthy cell relies on its mitochondria[1] (descendants of bacteria that took up residence in the single-celled ancestors of animals and plants about 2 billion years ago) to oxidise sugar molecules and release useful energy. Most cancer cells, however, use a less efficient mechanism called glycolysis[2] to power themselves. They thus cut their mitochondria out of the loop.

肿瘤细胞产生能量的方式极为特别。正常细胞依靠线粒体（是由大约20亿年前寄居在单细胞动植物祖先体内的细菌演化而来）氧化糖分子从而释放有用的能量，而大多数肿瘤细胞则通过糖酵解作用来为自身供能。这种作用机制效率较低，但不需要线粒体参与。

 

That cancer cells often rely on glycolysis was discovered by Otto Warburg in 1930. （2）But until recently the Warburg effect, as it has come to be known, was little more than a curiosity—and a contentious one at that[3]. Now, it looks a lot more interesting, for Evangelos Michelakis and his colleagues at the University of Alberta, in Canada, are testing a drug called dichloroacetate that suppresses the Warburg effect and reactivates the mitochondria. The result shows why mitochondrial suppression is so important to tumours: when they are unsuppressed, the tumour they are in stops growing.

肿瘤细胞通常依靠糖酵解供能是Otto Warburg于1930年发现的，但这一被后人称为“Warburg效应”的现象一直以来只是让人感到好奇而已，而且还颇有争议。现在，此效应引起了更多的关注——加拿大阿尔贝达大学的Evangelos Michelakis及其同事们正在试验一种名为二氯醋酸、能够抑制Warburg效应并激活线粒体的药物。为何线粒体抑制对肿瘤如此重要从试验结果可见一斑：当线粒体未受到抑制时，线粒体所在的肿瘤就会停止生长。

 

At first sight, this is all terribly paradoxical. Cancer cells multiply rapidly—and such multiplication requires a lot of energy. Normally, glycolysis is merely the prelude to energy production. It breaks glucose down into molecules called pyruvate that are fed to the mitochondria for processing. This breakdown yields some energy, but not much. （3）However, it does not require oxygen—a substance that cancer cells are frequently deprived of, as tumours often fail to develop the blood vessels needed to supply it.

乍一看，这似乎完全违反了常理。肿瘤细胞增殖迅速，且增殖过程需要大量能量。正常情况下，糖酵解只是能量产生过程的起始阶段，它使葡萄糖分解成丙酮酸分子，后者被线粒体摄取并加工。此分解过程产生了一定的能量，但并不多。不过，糖酵解无需氧气，而肿瘤细胞通常由于肿瘤无法生成供氧血管因而都处于缺氧状态。

 

Cancer cells seem to adjust so well to glycolysis that even if blood vessels do grow into a tumour and the oxygen thus returns, they stick with it.（4）From the cancer's point of view that is a very good choice, as one of the other jobs of the mitochondria is to kill a cell if it goes bad—a process known as apoptosis.

肿瘤细胞似乎很适应糖酵解作用，因此即使某个肿瘤内形成了血管并获得氧气，但肿瘤细胞仍继续利用糖酵解供能。对于肿瘤而言，这再好不过，因为线粒体另外还有一个功能，那就是当细胞衰老或受损时杀死细胞，即人们所熟知的细胞凋亡过程。

 

The role of dichloroacetate is to re-activate the mitochondria by stimulating an enzyme that feeds pyruvate into their energy-generating cycle. (The drug is already tested and approved for the treatment of certain mitochondrial diseases.) It seems this reactivation also allows the mitochondria to stimulate apoptosis.

二氯醋酸的作用是通过促进一种酶催化丙酮酸进入产能循环过程而重新激活线粒体。（该药物已经试验证实并得到政府许可用于治疗某些线粒体疾病。）表面上看，线粒体的重新激活同样会促进凋亡发生。

 

At least, that is what Dr Michelakis thinks is going on. His results are certainly reminiscent of those obtained last year by Valeria Fantin and Philip Leder of HarvardMedicalSchool. Dr Fantin and Dr Leder used a trick called RNA interference to modify glycolysis in the tumours of some specially bred laboratory mice.

不管怎样，Michelakis的想法得到了实现。他的结果自然让人们想起了去年哈佛医学院Valeria Fantin和Philip Leder所得到的结果。Fantin和Leder采用一种名为“RNA干扰”技术，对一些专门喂养的实验室小鼠体内肿瘤糖酵解作用加以了改进。

 

If too much pyruvate is being made, the surplus is normally turned into lactic acid. (（5）Athletes whose muscles demand more energy than their mitochondria can deliver suffer from a build-up of lactic acid as their glycolytic pathways go into overdrive. It is this build-up that causes cramp[4].) The RNA interference employed by Dr Fantin and Dr Leder stops the conversion of pyruvate into lactic acid, causing it to build up. Their hope was that, overwhelmed with pyruvate, the mitochondria would be forced to respond.

丙酮酸如果产生过多，多余的丙酮酸通常都会转化为乳酸。（运动员由于其肌肉所需能量超出线粒体供能水平，因此糖酵解途径就会过度运转，从而导致乳酸蓄积，后者又导致能量之源被切断。）Fantin 和Feder所采用的RNA干扰技术阻止了丙酮酸转化成乳酸，从而使其不断蓄积。他们希望，当丙酮酸大量蓄积时，线粒体就会被迫产生反应。

 

And respond they did. Apoptosis shot up in the treated animals. Dr Fantin and Dr Leder also observed a marked decline in tumour growth rates. The survival rate of animals went up, too. None of the members of an untreated control group survived the four-month period over which the experiment was conducted. By contrast, 80% of the treated animals survived.

情况的确不出所料。经RNA干扰技术处理的小鼠体内凋亡迅速增多，同时Fantin和Feder也发现肿瘤生长速度明显减缓，而小鼠存活率也得以提高。经过四个月的试验，未接受处理的对照组小鼠无一存活，而处理过的小鼠则有80%存活。

 

（6）RNA interference is the subject of eager investigation among pharmaceutical companies, but so far it has yet to yield a drug approved by the regulators. Dichloroacetate, by contrast, is already employed for other purposes. That does not mean it will work as an anti-cancer agent in the real world, of course. But it does give it a head start. And even if dichloroacetate itself does not work, Dr Michelakis's study points towards a new approach to stopping cancer in its tracks.

RNA干扰技术是制药公司热衷于研究的课题，但迄今为止还没有形成一种获得监管部门批准的药物。相比之下，二氯醋酸已得到推广应用。当然，这并非意味着二氯醋酸会成为一种可以用于临床的抗肿瘤药，但它的确具有领先意义，而且即使二氯醋酸本身不起作用，Michelakis的研究还是指引人们找到了阻止肿瘤生长的一个新方法。

[QUIZ]

英译汉（将划线部分英文翻译成中文）：

[NOTES](LONGMAN)

1. mitochondria n. 线粒体

2. glycolysis n. 糖酵解

3. at that 而且: That's an idea, and a good one at that. 那倒是个主意,而且是个好主意。

4. cramp 抽筋,痉挛[C][U]: The swimmer was seized with a cramp and had to be helped out of the water. 那个在游泳的人突然抽起筋来,让别人帮着上了岸。

5. head start 抢先起步的优势;有利的开端