A peptide derived from α-fetoprotein prevents the growth of estrogen-dependent human breast cancers sensitive and resistant to tamoxifen
A peptide derived from α-fetoprotein prevents the growth of estrogen-dependent human breast cancers sensitive and resistant to tamoxifen
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DOI：
10.1073/pnas.251667098
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发表时间：
2002-02-19
影响因子：
11.1
通讯作者：
Jacobson, HI
中科院分区：
文献类型：
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作者：
Bennett, JA;Mesfin, FB;Jacobson, HI
将来自甲胎蛋白的8-mer肽（EMTOVNOG）与他莫昔芬比较对植入免疫缺陷小鼠中的人乳腺癌异种移植物的生长的活性。肽和他莫昔芬都能阻止雌激素受体阳性MCF-7和T47 D人乳腺癌异种移植物的生长。MCF-7的亚系，通过在培养物中暴露于这种药物6个月而对他莫昔芬产生耐药性，被发现在体内对他莫昔芬具有耐药性。肽完全阻止了MCF-7的这种他莫昔芬抗性亚系的异种移植物生长。无论是肽还是他莫昔芬都不能有效减缓雌激素受体阴性MDA-MB-231人乳腺癌的异种移植生长。他莫昔芬的一个令人担忧的副作用是它对子宫的肥大作用。在这项研究中，他莫昔芬被证明可以刺激体内未成熟小鼠子宫的生长，并且肽显著抑制他莫昔芬的子宫营养作用。肽的作用机制与他莫昔芬不同，因为肽不干扰[H-3]雌二醇与雌激素受体的结合。总之，甲胎蛋白衍生肽似乎是一种新的药物，干扰他莫昔芬敏感以及他莫昔芬耐药的雌激素受体阳性人乳腺癌的生长，它抑制他莫昔芬的子宫副作用，因此，它可能是有用的组合或代替他莫昔芬治疗雌激素受体阳性人乳腺癌。
An 8-mer peptide (EMTOVNOG) derived from a-fetoprotein was compared with tamoxifen for activity against growth of human breast cancer xenografts implanted in immune-deficient mice. Both peptide and tamoxifen prevented growth of estrogen-receptor-positive MCF-7 and T47D human breast cancer xenografts. A subline of MCF-7, made resistant to tamoxifen by a 6-month exposure to this drug in culture, was found to be resistant to tamoxifen in vivo. Peptide completely prevented the xenograft growth of this tamoxifen-resistant subline of MCF-7. Neither peptide nor tamoxifen was effective in slowing the xenograft growth of the estrogen-receptor-negative MDA-MB-231 human breast cancer. A worrisome side effect of tamoxifen is its hypertrophic effect on the uterus. In this study, tamoxifen was shown to stimulate the growth of the immature mouse uterus in vivo, and the peptide significantly inhibited tamoxifen's uterotrophic effect. The mechanism of action of peptide is different from that of tamoxifen in that the peptide does not interfere with the binding of [H-3]estradiol to the estrogen receptor. In conclusion, alpha-fetoprotein-derived peptide appears to be a novel agent that interferes with the growth of tamoxifen-sensitive as well as tamoxifen-resistant estrogen-receptor-positive human breast cancers; it inhibits the uterotrophic side effect of tamoxifen and, thus, it may be useful in combination with or in place of tamoxifen for treatment of estrogen-receptor-positive human breast cancers.