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【medical-news】前列腺癌细胞如何抗拒死亡？
Winston-Salem, N.C. -- New findings about how prostate cancer cells are able to resist hormone treatment and defy death may lead to more effective drug treatments, according to researchers from Wake Forest University School of Medicine and colleagues.
"We hope this will lead to new treatments or ways to monitor treatment to make sure it's having its intended effect," said George Kulik, Ph.D., D.V.M., assistant professor of cancer biology and senior researcher.
The goal of the research was to uncover how prostate cancer cells become resistant to treatment that lowers levels of male hormones such as testosterone, which the cells normally need to survive. They found that a protein known as BAD is involved in three different survival strategies used by the cancer cells. Their results are published in the July 28th issue of the Journal of Biological Chemistry.
"The normal response of prostate cells when male hormones are blocked is cell death," said Kulik. "The cancer cells find a way to resist the treatment and we wanted to discover the mechanism."
Treatments for prostate cancer include surgery, radiation therapy and hormone therapy, also known as androgen ablation therapy because it reduces levels of the male hormones that can stimulate the growth certain types of prostate cancer. Lowering hormone levels makes prostate cancer shrink or grow more slowly. It is considered the most efficient systemic therapy for prostate cancer. However, nearly all prostate cancers become resistant to this treatment over time.
The researchers evaluated three different pathways involved in cell signaling, the complex system of communication that governs cell actions. It had previously been shown that three pathways (activated by vasoactive intestinal peptide, epidermal growth factor or phosphoinositide 3-kinase) are known to be involved in cell survival. The goal of the researchers was to learn how these pathways are involved in the cancer cells resisting death. They found that all three signaling pathways work by inactivating a protein known as BAD that causes cell death.
Kulik said it appears that each of the three molecules is separately capable of inactivating BAD, which means that prostate cancer cells have three redundant survival mechanisms.
"Our findings suggest that BAD is an important switch in the development and growth of prostate cancer," said Kulik.
Next, the researchers hope to conduct animal studies to test their findings.
"If our finding is confirmed in animals and in human tumors, there are important implications for therapy," said Kulik.
For example, scientists could develop a drug to prevent BAD from being inhibited. Or, they could use the findings to test current drugs designed to block the effects of PI3K, one of the molecules. This would involve monitoring the status of BAD to see if the drugs were having their intended effects.
According to the American Cancer Society, prostate cancer is the most common type of cancer found in American men, other than skin cancer. The society estimates that there will be about 234,460 new cases of prostate cancer in the United States in 2006. About 27,350 men will die of this disease. Prostate cancer is the third leading cause of cancer death in men, after lung cancer and colorectal cancer. 终于抓住一个了！我认领了！12h后交卷！ 前列腺癌细胞如何抗拒死亡？
美国北卡罗莱纳州温斯顿-萨兰姆市(Winston-Salem, N.C.) 的Wake Forest 大学医学院研究人员，最近研究发现了前列腺癌细胞如何能够抵抗激素治疗并避免死亡的机理，因此可能找到更有效的药物治疗方法。
肿瘤生物学药学博士,兽医博士,副教授George Kulik博士说：“我们希望此项发现能够导致新的治疗手段的出现或者有新的方法去监测治疗结果的有效性。”
此项研究的目的是揭示前列腺癌细胞抵制降低男性激素（如睾酮）治疗的机理，而细胞的生存正常情况下是需要男性激素的。他们发现肿瘤细胞采用了三种生存策略，其中有一种已知的BAD蛋白也参与其中。这项研究成果发表在7月28日的生物化学杂志(JBC)上。
Kulik博士说：“前列腺细胞对男性激素的正常反应是细胞死亡，但肿瘤细胞却能想方设法生存下来，于是我们想发现其中的机制。”
前列腺癌的治疗包括手术切除，放射疗法和激素治疗，后者即雄激素去势疗法，它使男性激素水平降低。因为男性雄激素能刺激某些类型前列腺癌的生长，而降低性激素水平可使前列腺癌组织萎缩或生长减慢。这曾被认为是最有效的系统治疗前列腺癌的方法。然而，随着时间的过去，现在几乎所有的前列腺癌都对激素治疗产生了抵抗。
研究人员评估了三种不同的信号通路，这些通路参与了控制细胞信号传导以及管理细胞活动的复杂传导系统。这三种已知的通路与细胞生存有关，它们被血管活性肠肽、表皮生长因子或者磷酸肌醇3激酶激活。研究人员试图探索清楚这些通路如何参与肿瘤细胞抵抗死亡的。他们发现这三种信号通路能灭活一种已知的能导致细胞死亡的BAD蛋白。
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作者:admin@医学,生命科学 2011-02-25 17:14
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