Study on effects of insulin-like growth factor on growth of prostate cancer

胰岛素样生长因子- i （Insulin-like growth factor- i, IGF-I）是一种强效的促有丝分裂和诱导分化的多肽生长因子，被认为是参与正常和恶性组织细胞增殖的重要自分泌-旁分泌因子。近年来，igf - 1受体在人正常前列腺上皮细胞、增生性前列腺细胞和大鼠前列腺癌细胞中均有发现。此外，IGF结合蛋白家族（IGF binding proteins, igfbp）至少包含6种与IGF具有高结合亲和力的蛋白，它们是不同形式的IGF受体，被认为控制IGF的增殖和有丝分裂作用。使用雄激素依赖性前列腺癌细胞LNCaP-FGC （FGC）及其衍生的雄激素非依赖性亚系LNCaP-r和LNO，以及雄激素非依赖性细胞系pc -3和TSU- pri （TSU）。乳腺癌细胞系MCF-7作为IGF反应性的对照细胞系。igf - 1或雄激素对生长的影响更多的细胞是通过使用基于四氮唑盐MTT酶还原的测试来评估的。在十二烷基硫酸钠-聚丙烯酰胺凝胶上分离条件培养基蛋白，转移到硝化纤维素纸上，用Western blotting检测igfbp。通过饱和分析测定制备膜中IGF-I受体的含量。数据采用多点Scatchard分析法计算。IGF-I刺激MCF-7细胞呈剂量依赖性（1-100ng/ml）。在相同条件下，FGC、LNCaP-r、LNO和PC-3细胞系对IGF-I没有反应，而IGF-I对TSU细胞系的生长有轻微的刺激作用。在igf - 1的基础上添加雄激素对依赖于青蛙的FGC细胞系的细胞生长没有影响。igf - 1受体在所有细胞系中均表现出高亲和力，FGC细胞系的受体含量低于其他雄激素非依赖性细胞系。所有前列腺癌细胞株均分泌IGFBP-2，而在LNCaP-r、PC-3和TSU培养基中也检测到IGFBP-3和/或IGFBP-4。尽管存在高亲和力的IGF受体，但除了一个例外（TSU）， IGF- 1对前列腺癌细胞系的细胞增殖没有影响。正如对其他组织的描述，IGFBP-2可能是抑制这些细胞系中IGF-I生物活性的因素，而其他一些igfbp，如IGFBP-4可能增强细胞对IGF-I的反应性。因此，igfbp调节igf - 1介导的前列腺癌细胞增殖。少

Insulin-like growth factor-I (IGF-I) is a potent mitogenic and a differentiation inducing polypeptide growth factor, and is considered to be a significant autocrine-paracrine factor involved in cellular proliferation of normal and malignant tissues. Recently, IGF-I receptors have been characterized in human normal prostate epithelial cells, hyperplastic prostate cells, and rat prostate cancer cells. Furthermore, a family of at least six proteins with high binding affinity for IGFs, the IGF binding proteins (IGFBPs), are described which are different form IGF receptors and are considered to control the proliferative and mitogenic effects of IGFs.The androgen-dependent prostatic carcinoma cell line, LNCaP-FGC (FGC), its derived androgen-independent sublines, LNCaP-r and LNO,and the androgen-independent cell lines PC-3and TSU-PRI (TSU) were used. The breast cancer cell line MCF-7 cell line served as control cell line for IGF responsiveness. The effects of IGF-I or androgens on the growth … More of the cells were assessed by the use of a test based on the enzymatic reduction of the tetrazolium salt MTT.Conditioned medium proteins were separated on sodium dodecylsulfate-polyacrylamide gel and transferred to nitrocellulose paper and IGFBPs were detected by Western blotting. IGF-I recceptor content of membrane preparated was determined by saturation analysis. The data were calculated by multiple-point Scatchard analyzes.IGF-I stimulated MCF-7 cells dose-dependently (1-100ng/ml). Under the same conditions FGC,LNCaP-r, LNO,and PC-3 cell lines did not respond to IGF-I,whereas it slightly stimulated growth of the TSU line. Androgen addition to IGF-I did not influence the cell growth of the andfrogen-dependent FGC cell line. High affinity IGF-I receptors were demonstrated in all cell lines lested, the receptor content of the FGC line being lower than the other androgen-independent cell lines. All prostatic cancercell lines secreted IGFBP-2, whereas IGFBP-3 and/or IGFBP-4 were also detected in the medium of LNCaP-r, PC-3 and TSU cultures.In spite of the presence of high affinity IGF receptors, with one exception (TSU), IGF-I had no effect on cell proliferation of the prostatic cancer cell lines tested. As has been described for other tissues, IGFBP-2 may be a factor that inhibits the biological activity of IGF-I in these cell lines, whereas some other IGFBPs, such as IGFBP-4 may enhance IGF-I responsiveness of the cells. It is therefore suggested that IGFBPs regulate IGF-I mediated cell proliferation of prostate cancer cells. Less