降胆固醇药物可延缓前列腺肿瘤的生长

研究将低胆固醇与较少血管的前列腺肿瘤联系在一起

2009年2月23日

波士顿，大众。保持胆固醇一项研究表明，在检查中的水平可能不仅有利于心脏健康，但也可能延缓前列腺癌的进展波士顿儿童医院。 When mice with human prostate tumors were fed a no-胆固醇 diet in combination with the 胆固醇-lowering drug ezetimibe (Zetia, Schering-Plough), tumor growth was slowed。

这项研究发表于3月刊美国病理学杂志，也发现肿瘤的急剧减少血管生成—blood-vessel growth within the tumors—in the mice with the lowest 胆固醇 levels, suggesting that ezetimibe retards prostate tumor growth at least in part by inhibiting tumor 血管生成。

The researchers compared four groups of animals--two fed the high-胆固醇 diet, with or without ezetimibe, 和 two fed a no-胆固醇 diet, with or without the drug。 "We were initially interested to find out whether raising 胆固醇 would accelerate the rate of tumor growth 和 whether reducing 胆固醇 would reduce the growth of tumors," says基思，博士，各部门矫形外科和泌尿科at Children's, 和 the paper's first author。

Two weeks after tumor implantation, tumors were largest in the animals fed the high-胆固醇 diet (averaging 0。88 grams per tumor site), 和 smallest in those on the no-胆固醇 diet plus the drug (averaging 0。63 grams per tumor site)。

But there was also a marked difference in 血管生成。 "The thing that caught my attention almost immediately was that when we were harvesting the tumors, there was a great deal more blood in some of the tumors than others," says Solomon。 "I didn't even know which groups the tumors were coming from。 Then we started to look at this, 和 found some real group differences that went along with the growth curves。"

Staining of the tumors for the endothelial cells that line blood vessel walls showed there was approximately 50 percent more tumor 血管生成 in the untreated high-胆固醇 group than in the groups receiving ezetimibe, regardless of which diet they were on。 Higher levels of 胆固醇 correlated with increased 血管生成。

"This was something we did not anticipate at the beginning of this study," says Solomon。 "We hypothesized that the tumors would be bigger or smaller based on the diet 和 the drug, but we did not hypothesize that it would be related to the degree of 血管生成。"

"The anti-angiogenic effect of 胆固醇 lowering implies that these findings may have relevance to other tumor types, " says米迦勒Freeman博士, of Children's Department of 泌尿科, senior author of the study。

Cholesterol is synthesized in all areas of the body, but the prostate makes it at a relatively high rate 和 loses the ability to control 胆固醇 levels as the body ages。 High-胆固醇 diets likely contribute to the excess 胆固醇 in the aging prostate, 和 may exacerbate disease incidence 和 progression, Solomon says。 Prostate tumors have been shown to contain significant amounts of 胆固醇。

"I would speculate that the 胆固醇 is giving the tumor cells, 和 cells in the surrounding environment, material to encourage 血管生成 和 growth," explains Solomon。 "If you blocked tumor cells from synthesizing 和 taking up 胆固醇, they would die。 Without 胆固醇, there is no growth。"

Prostate cancers are usually very slow-growing 和 many men can live for many years with prostatic tumors before dying of unrelated causes。 Solomon speculates that if people aggressively manage their 胆固醇 levels throughout their lives, it might delay first appearance of medically significant prostate disease by approximately 10 years 和 may even reduce their appearance overall。

"A 20 to 30 percent reduction in 胆固醇 might not affect a fast-growing tumor, but could have a significant effect on a slow-growing tumor," says Solomon。 "It could mean that men who now have to undergo procedures may be able to avoid irritating, painful, 和 stressful treatments。 It could save lives, money 和 quality of life because once men have surgery to remove their prostate, they are often left impotent 和 incontinent。"

Population studies have linked prostate cancer with high 胆固醇 levels 和 Western diets high in 胆固醇。 In 2005, the Solomon 和 Freeman groups showed that 胆固醇 helps prostate tumors survive 和 grow at the cellular level by altering chemical signaling patterns。

The researchers now hope to further explore the relationship between 胆固醇 和 its role in prostate tumor 血管生成 和 growth。 "This has important implications not only for treatment of prostate tumors but also for the treatment of other cancers," says Solomon。

这项研究是由国家健康研究院和 the美国国防部。

接触：
Rob格雷厄姆
波士顿儿童医院
617-919-3110
rob。graham@childrens。harvard。edu

波士顿儿童医院 is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children 和 adults since 1869。 More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine 和 12 members of the Howard Hughes Medical Institute comprise Children's research community。 Founded as a 20-bed hospital for children, 波士顿儿童医院 today is a 397-bed comprehensive center for pediatric 和 adolescent health care grounded in the values of excellence in patient care 和 sensitivity to the complex needs 和 diversity of children 和 families。 Children's also is the primary pediatric teaching affiliate of Harvard Medical School。 For more information about the hospital 和 its research visit:www。childrenshospital。org/newsroom。

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