胰腺癌治療新突破：抗氧化劑是如何殺死胰腺癌細胞的！

Antioxidant suppression eradicates pancreatic cancer cell

抗氧化劑的抑制作用能夠清除胰腺癌細胞

A novel drug therapy - that mimics the suppression of an antioxidant-promoting protein - kills pancreatic cancer cells, new research reveals.

一種新的研究揭示了，有一種新的藥物治療——模擬抗氧化劑的抑制作用——促進蛋白——能夠殺死胰腺癌細胞。

According to the American Cancer Society, around 53,070 people will be diagnosed with pancreatic cancer in the Unites States in 2016, and around 41,780 people will die of the disease. Pancreatic cancer accounts for about 3 percent of all cancers in the U.S. and about 7% of cancer deaths.

根據美國癌症學會的數據，2016年，在美國越有53070名患者被確證為胰腺癌，有41780位患者死於該病。在美國，胰腺癌約佔所有癌症的3%，以及占癌症死亡的7%。

Pancreatic cancer is caused by the abnormal, uncontrolled growth of cells in the pancreas.

A research team at Cold Spring Harbor Laboratory (CSHL) in New York finds that reducing levels of antioxidants in pancreatic cells can help to kill them. This new strategy for eradicating pancreatic cancer cells may open new doors for treating this serious illness, in which less than 5 percent of patients survive 5 years.

胰腺癌是由胰腺細胞變異、不受控制生長而造成的。位於紐約的冷泉港實驗室（CSHL）的一隻研究小組發現，減少胰腺細胞中抗氧化劑的水平能夠幫助殺死他們。這個清除胰腺癌細胞的新策略，為治療這種惡性疾病打開了新世界的大門。須知道，這種罹患這種疾病的患者5年存活率低於5%。

"Antioxidant" has become a popular buzzword that is viewed as a cure-all notion for health ailments; it is widely believed that raising levels of antioxidants stops cancer cells from developing.

「抗氧化劑」已成為一個能治癒所有疾病的熱詞；大家都認為抗氧化劑水平的提高有利於阻止癌細胞的增長。

In reality, although antioxidants interact with and neutralize free radicals and prevent them from causing damage, there is little available evidence that antioxidants prevent cancer.

實際上，儘管抗氧化劑同遊離基之間會產生反應且能中和自由基，也可以阻止其產生損害，但幾乎沒有證據證明抗氧化劑能阻止癌症。

Furthermore, trials have found that people taking antioxidant supplements during cancer therapy have worse outcomes, especially if they were smokers.

而且，實驗表明患者在治療癌症期間服用抗氧化劑產生的效果可能更糟，尤其是吸煙人群。

Does increasing antioxidant levels do more harm than good?

增加抗氧化劑的水平弊大於利嗎？

In a series of complex experiments, the CSHL researchers demonstrate that in pancreatic cells that are abnormal or in a malignant state, raising antioxidant levels can do more harm than good.

在一系列的複雜實驗中，CSHL的研究者展示說在胰腺非正常細胞或惡性細胞中增加抗氧化劑的水平造成的損害大於益處。

In healthy cells, the amounts of oxidizing and anti-oxidizing agents are kept precisely balanced in every cell.

在健康細胞中，每個細胞中氧化和抗氧化物質保持著精確的平衡。

However, in proliferating cancer cells - that are increasing rapidly in number through growth and cell division - the amounts of oxidants in malignant cells increase, but anti-oxidants also increase to counter the impact of rising oxidation.

然而，在增殖的癌細胞中——通過細胞生長和細胞分裂在數量上迅速增長——惡性細胞中氧化劑的數量是在增長的，同時抗氧化劑也在增長，來對氧化劑增長所帶來的衝擊。

CSHLs Prof. David Tuveson - M.D., Ph.D., director of research for the Lustgarten Foundation - and colleagues note that without the amounts of antioxidants going up in scale with the oxidants, malignant cells will die from excessive oxidation.

CSHL教授David Tuveson – M.D.、Ph.D.、勒斯特加滕基金會研究主任 – 和他的同事們注意到，如果抗氧化劑的數量沒有同氧化劑成比例地增長，惡性細胞會因為氧化劑過量而死亡。

"Of course, thats exactly what we want cancer cells to do - to burn themselves out," says Iok In Christine Chio, a postdoctoral investigator in the Tuveson lab who led the experiments.

博士後研究員，也是勒斯特加滕實驗室項目帶頭人Iok In Christine Chio說「當然，這正是我們試圖讓癌細胞發生的動作 – 將它自己燒死。」

"The therapeutic principle our lab is testing is whether, by increasing the level of oxidation in cancer cells, we can cause pre-malignant and malignant cells to die," she adds.

她還說：「我們在實驗室的治療原則是，測試在惡性細胞中增加氧化劑的數量能否導致惡性細胞或將要惡化的細胞死亡。」

Excessive oxidation causes cells to commit suicide

過量的氧化劑可使細胞自殺

Treatments for cancer such as radiation therapy and chemotherapy destroy cancer cells by promoting oxidation. Although antioxidants protect cellular DNA from damage by oxidative stress, they likely protect cancer cells, too.

放療和化療都是通過促使細胞中的氧化劑增量來消滅癌細胞的。儘管抗氧化劑能夠通過氧化應激反應來保護細胞核中的DNA不受損害，但它同時也可以保護癌細胞。

Exposing cells to excessive oxidation causes them to experience programmed cell death called apoptosis. A method of increasing oxidation in cancer cells is to decrease levels of antioxidants within the same cells.

將細胞暴露給氧化劑可使其按一定程序死亡的過程叫細胞凋亡。有一種增加癌細胞中氧化劑的方法就是降低同一細胞中抗氧化劑的水平。

Tuveson and team aimed to find a technique whereby they could increase oxidation without harming healthy cells. They concentrated on NRF2, a protein that can be tweaked to disrupt the balance between oxidation and decreased cancer cells.

Tuveson和他的團隊的研究目的就是，找到一種能夠增加氧化劑還不傷害健康細胞的技術。他們將注意力集中在NRF2上，一種能夠通過微調來打亂氧化劑間平衡，從而減少癌細胞的蛋白。

When NRF2 is active, cells synthesize a chemical called glutathione, an important antioxidant. However, it is not possible to reduce NRF2 activity or make it inactive, as it has a role in regulating several hundred different genes. "One cant delete it from a cell without impacting many other processes," says Chio.

當NRF2活躍時，細胞能合成一種化學物質叫谷胱甘肽，一種重要的抗氧化劑。然而，想要減少NRF2的活性或使其失活是不可能的，因為這種蛋白需要調節幾百種基因。Chio說「如果試圖將這種蛋白從細胞中刪除又不影響其它作用是不可能的。」

The team used samples of pancreas cells from people with pancreatic cancer (malignant and pre-malignant) and individuals with a healthy pancreas to conduct an experiment where NRF2 was eliminated.

研究團隊用在胰腺癌患者身上提取的胰腺細胞（患病細胞和將患病細胞）和健康人身上提取的胰腺細胞做了實驗，將NRF2從中排除。

Normal pancreas cells not harmed by two-drug treatment

正常胰腺細胞不會被兩種藥物聯和治療損害

They found that when NRF2 was missing, the process of translating messages from the genes into proteins was highly affected by the oxidant and antioxidant balance, but only in the cancerous cells. The healthy cells were still able to produce the proteins.

他們發現當NRF2消失時，將基因信息翻譯變成蛋白質的過程在很大程度上受氧化劑和抗氧化劑之間平衡的影響，但僅限於癌細胞。正常的健康細胞仍然能產生蛋白。

"We were very excited when we saw this. This meant that if we could find a way of reducing antioxidants, protein synthesis would only be impacted in precancerous and malignant cells, a potentially powerful therapeutic strategy."

「我們發現這點後特別興奮。這意味著，如果我們有辦法減少抗氧化劑的量，蛋白質合成只在癌症前期細胞和患病細胞中受影響，這是一種潛力很大的治療方法。」

The crux of the experiment was to use two drugs in combination: an AKT (protein kinase B) inhibitor, and a BSO (buthionine sulfoximine), which reduces levels of glutathione.

實驗的核心是兩種藥物聯用：一種AKT（蛋白質激酶B）抑製劑，和一種BSO（丁硫氨酸亞碸胺），可以減少谷胱甘肽的水平。

AKT inhibitors have been used in trials on cancer patients before but with limited success. The team wanted to combine this with the BSO to mimic what would happen if they could reduce levels of NRF2.

AKT抑製劑以前在癌症患者身上做過實驗，但效果有限。研究團隊試圖將其同BSO聯用，如果在他們能減少NRF2水平的情況下，看能發生什麼情況。

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