Prévost G, Foehrlé E, Thomas F, Pihan I, Veber N, Starzec A, Israël L
Institut d'Oncologie Cellulaire et Moléculaire Humaine, Bobigny, France.
Endocrinology. 1991 Jul;129(1):323-9. doi: 10.1210/endo-129-1-323.
Somatostatin has been shown to lower plasma levels of various hormones and growth factors involved in regulation of the growth of human breast cells. In the present study we examined the ability of the somatostatin octapeptide analog BIM23014 to modulate the in vitro growth of five human breast cell lines: HBL100, Hs578T, MDAMB231, T47D, and MCF7. BIM23014 inhibited the growth of the two steroid-dependent cell lines, MCF7 and T47D, in a dose-related manner. This inhibitory effect was only observed when MCF7 and T47D cells were cultivated in medium containing steroid-depleted serum. The growth of a MCF7 variant capable of growth in serum-free medium was also inhibited by BIM23014, indicating that serum factors are not required for this inhibition. In the serum-free medium, the addition of estradiol before or during treatment with BIM23014 abolished its inhibitory effects on cell growth. The studies including time course, competitive inhibition, and cross-linking of iodinated BIM23014 to its receptor revealed a specific binding on MCF7 cells and showed a single 57,000 mol wt protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results support the hypothesis that BIM23014 inhibits the growth of steroid-receptor positive cells of human breast cancers through its own receptor in estradiol-free conditions.
生长抑素已被证明可降低参与人类乳腺细胞生长调节的各种激素和生长因子的血浆水平。在本研究中,我们检测了生长抑素八肽类似物BIM23014调节五种人类乳腺细胞系(HBL100、Hs578T、MDAMB231、T47D和MCF7)体外生长的能力。BIM23014以剂量相关的方式抑制了两种类固醇依赖性细胞系MCF7和T47D的生长。只有当MCF7和T47D细胞在含有类固醇缺乏血清的培养基中培养时,才观察到这种抑制作用。BIM23014也抑制了能够在无血清培养基中生长的MCF7变体的生长,这表明这种抑制作用不需要血清因子。在无血清培养基中,在BIM23014处理之前或期间添加雌二醇可消除其对细胞生长的抑制作用。包括时间进程、竞争性抑制以及碘化BIM23014与其受体交联在内的研究揭示了其在MCF7细胞上的特异性结合,并在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳中显示出一条单一的57,000道尔顿分子量的蛋白带。这些结果支持了以下假设:BIM23014在无雌二醇的条件下通过其自身受体抑制人类乳腺癌类固醇受体阳性细胞的生长。