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针对病种:垂体瘤

发表时间:1997年7月

发表国家:美国

登载刊物:临床内分泌学与代谢杂志

研究单位:英国皇家Hallamshire医院

研究人员:琼斯等

主要结论:金雀异黄素通过抑制酪氨酸激酶活性发挥对人垂体瘤细胞的生长抑制作用.

J Clin Endocrinol Metab. 1997 Jul;82(7):2143-7.
Suppression of tyrosine kinase activity inhibits [3H]thymidine uptake in cultured human pituitary tumor cells
Jones TH, Justice SK, Price A.
(Royal Hallamshire Hospital)

Tyrosine kinases are involved in the phosphorylation of proteins that regulate cell growth and proliferation. The mitogenic effect of several growth factors requires tyrosine kinase activity of their receptors. The effect of inhibition of tyrosine kinase activity on thymidine uptake into cultured human pituitary adenoma cells was studied using two inhibitors, genestein and methyl-2,3-dihydroxycinnamate (MDHC). Of 33 pituitary adenomas, 7 incorporated sufficient [3H]thymidine to be investigated in the experiments. Genestein and MDHC both potently inhibited thymidine uptake into these tumors, with a mean inhibition by 74 mumol/L genestein of 61.96 +/- 18.96% (+/- SD inhibition of basal), by 740 mumol/L genestein of 92.65 +/- 8.59%, and by 100 mumol/L MDHC of 93.84 +/- 3.85%. The 7 pituitary adenomas were all large with suprasellar extension and secreted interleukin-6 in vitro.They included 2 prolactinomas, 1 somatotropinoma, 1 mammosomatropinoma, and 3 clinically nonfunctioning adenomas. Epidermal growth factor stimulated thymidine uptake in 2 of the 3 clinically nonfunctioning adenomas studied, and this stimulation was inhibited by genestein. Both of these tumors released FSH in cell culture and are probably silent gonadotropinomas. The growth stimulatory effect of conditioned medium from human pituitary cell culture on GH3 cells was inhibited by both genestein and MDHC. We conclude that tyrosine kinase activity is crucial for the integrity and growth of pituitary adenomas in culture. Growth factors released by pituitary adenomas potentially may maintain and promote tumor growth by stimulating tyrosine kinase activity.

美国《临床内分泌学与代谢杂志》1997年7月
酪氨酸激酶抑制剂(金雀异黄素)抑制体外培养的 人垂体瘤细胞对 [3H] 胸苷的摄取
琼斯等
(英国皇家Hallamshire医院)

酪氨酸激酶(金雀异黄素)可调节与细胞生长和增殖相关的蛋白质磷酸化,多种生长因子的促有丝分裂作用需要酪氨酸激酶活化他们的受体。我们使用两种抑制剂金雀异黄素和甲基-2,3-二羟基肉桂酸(MDHC)研究酪氨酸激酶抑制剂抑制人垂体瘤垂体瘤细胞对 [3 H] 胸苷的摄取作用。33种垂体腺瘤中,选用7 种已摄入足够 [3 H] 胸苷的垂体腺瘤细胞进行研究。 
金雀异黄素 和 MDHC 都能有力抑制这些肿瘤取胸苷,平均抑制率分别为:74 微摩尔/升金雀异黄素为61.96 + /-18.96%(+ /-SD 基本抑制),740微摩尔/升金雀异黄素为92.65 + /-8.59%,以及 100 微摩尔/升MDHC为93.84+ /-3.85 %。在体外,这7种垂体腺瘤大部分都与蝶鞍上的扩展和分泌白细胞介素-6 有关。他们包含2种催乳素瘤、1种生长激素瘤、1 种乳腺瘤,和3种临床无功能腺瘤。表皮生长因子刺激2 /3 临床无功能腺瘤摄取胸苷,这种作用可与被金雀异黄素抑制。这些肿瘤在细胞培养中释放FSH,这可能是缘于沉默的促性腺素瘤。金雀异黄素和 MDHC 都能抑制人垂体细胞条件培养液对GH3 细胞生长刺激作用。 
我们的结论是酪氨酸激酶活性对的垂体瘤的完整性和程序化生长至关重要。垂体腺瘤释放的生长因子刺激酪氨酸激酶活性可保持和促进肿瘤生长,而金雀异黄素通过抑制酪氨酸激酶活性发挥对人垂体瘤细胞的生长抑制作用。

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