p38 MAPK通路特异性抑制剂SB203580对大鼠垂体GH3细胞增殖和分泌的影响

Effects of p38 Mitogen-activated Protein Kinase Inhibitor SB203580 on Proliferation and Growth Hormone Secretion of Rat Pituitary GH3 Cells

目的观察p38 MAPK通路特异性抑制剂SB203580对生长激素腺瘤GH3细胞增殖和分泌的影响,以探索p38 MAPK通路作为生长激素腺瘤潜在治疗靶点的可行性。方法 MTT实验检测不同浓度SB203580处理生长激素腺瘤GH3细胞24、48和72 h后细胞增殖活力。不同浓度的SB203580处理生长激素腺瘤GH3细胞72 h后经Annexin V-FITC/PI双染,流式细胞仪分析细胞凋亡的情况。ELISA检测不同浓度的SB203580处理生长激素腺瘤GH3细胞72 h后细胞上清中生长激素的分泌水平。结果 SB203580能够有效抑制生长激素腺瘤GH3细胞的增殖(P <0.05),并呈现良好的时间依赖性与浓度依赖性。不同浓度的SB203580能够显著诱导生长激素腺瘤GH3细胞凋亡(P <0.05)。SB203580处理泌生长激素腺瘤GH3细胞可显著降低生长激素水平(P <0.05),呈现良好的浓度依赖性。结论 p38 MAPK通路特异性抑制剂SB203580可抑制生长激素腺瘤GH3增殖和生长激素分泌,并能促进细胞凋亡。

Objective To observe the effects of p38 mitogen-activated protein kinase inhibitor SB203580 on proliferation and growth hormone secretion of rat pituitary GH3 cells and explore the p38 MAPK pathway as a potential therapy target for growth homone adenoma. Methods After treated with different concentrations of SB203580 for 24, 48, 72 h, the proliferation of rat pituitary GH3 cells was determined by MTT. The apoptosis levels were measured by Annexin V/PI. And the expression of growth hormone levels in the supernatant of GH3 cells treated with increasing concentrations of SB203580 for 72 h were measured by ELISA. Results SB203580 caused significant cytotoxicity in GH3 cells with a concentration- and time-dependent manner. Treatment with SB203580 induced GH3 cells apoptosis in a concentration-dependent manner （P 〈0.05）. In addition, the level of growth hormone was significantly decreased in the supernatant of GH3 cells after exposure to SB203580 （P 〈0.05）. Conclusion p38 mitogen-activated protein kinase inhibitor SB203580 may inhibit the proliferation and growth hormone secretion of rat pituitary GH3 cells.