IL-2对培养的人垂体腺瘤细胞增殖的影响及其机制

目的:研究IL-2对人垂体腺瘤细胞的增殖、细胞周期、细胞内蛋白激酶C(PKC)及cAMP/cGMP的影响,并探讨其作用的机制。方法:采用MTT比色法和3H-TdR掺入法检测IL-2对人垂体腺瘤细胞增殖和DNA合成的影响;用流式细胞术检测IL-2对垂体腺瘤细胞细胞周期的影响。用放射免疫测定法检测PKC的活性及cAMP和cGMP的含量。结果:(1)IL-2可促进垂体腺瘤细胞增殖和DNA合成,且呈剂量依赖性。(2)IL-2可显著降低垂体腺瘤细胞G1期的细胞比率,而增加S期和G2期的细胞比率。(3)与空白处理组相比较,使用PKC的激动剂PMA处理培养的人垂体腺瘤细胞,可使胞膜和细胞总PKC升高;而用IL-2(1×105U/L)处理后,胞质、胞膜和细胞总PKC的活性均升高。(4)IL-2(5×104、1×105U/L)作用于人垂体腺瘤细胞后,胞内cAMP浓度显著降低;而cGMP的浓度没有明显改变。结论:IL-2对垂体腺瘤细胞增殖分化的调控作用是细胞内多信息系统相互整合的结果。

Influence of IL-2 on proliferation of cultured human pituitary adenoma cells and its mechanism

AIM: To investigate the effects of IL-2 on the proliferation, cell cycle, protein kinase C(PKC) and cAMP/cGMP of cultured human pituitary adenoma cells. METHODS: MTT colorimetry, (3)H-TdR and flow cytometry were used to detect the proliferation and radioimmunoassay was used to observe the effect of IL-2 on PKC activity and cAMP/cGMP levels of cultured human pituitary adenoma cells. RESULTS: (1) IL-2 (1 x 10(4), 1 x 10(5) and 5 x 10(5) U/L) stimulated the proliferation and DNA synthesis of cultured human pituitary adenoma cells in a dose-dependent manner. (2) IL-2 (1 x 10(4), 1 x 10(5) and 5 x 10(5) U/L) decreased the ratio of pituitary adenoma cells in G(1) phase and increased the ratio in S and G(2) phase markedly. (3) Compared with control, PMA, a PKC activator, increased the activity of membrane and total PKC in human pituitary adenoma cells. However, after treatment with IL-2 (1 x 10(5) U/L), a significant increase of the activity of cytoplasmic, membrane and total PKC in human pituitary adenoma cells was observed. (4) IL-2 (5 x 10(4), 1 x 10(5) U/L) decreased the amount of cAMP in the cytoplasm of human pituitary adenoma cells, but had no effect on that of cGMP. CONCLUSION: IL-2 can stimulate the proliferation of pituitary adenoma cells through PKC and cAMP/cGMP signaling pathways.