链脲佐菌素对人神经母细胞瘤系SH-SY5Y细胞生长的影响

Effect of streptozotocin on the growth of human neuroblastoma SH-SY5Y cells

目的研究体外链脲佐菌素(STZ)对人神经母细胞瘤(SH-SY5Y)细胞生长以及SH-SY5Y细胞胰岛素信号转导通路相关蛋白表达的影响。方法采用MTT测定法测定SH-SY5Y细胞活性,乳酸脱氢酶(LDH)漏出率测定法观察SH-SY5Y细胞生长情况;应用Western blot法检测胰岛素信号转导通路相关蛋白胰岛素受体-1(IRS-1)、磷脂酰肌醇激酶-3(PI3K)等的改变。结果 STZ与SH-SYSY细胞共同孵育可抑制SH-SY5Y细胞生长,阻断胰岛素对SH-SY5Y细胞的促生长作用,且STZ抑制细胞生长呈明显的时间-剂量效应。随STZ浓度增加,LDH漏出率也增加。Western blot半定量分析发现IRS-1、PI3K表达减少。结论体外STZ与SH-SY5Y细胞共孵育可能影响胰岛素/胰岛素样生长因子-1信号转导系统对细胞的促生长作用。STZ与SH-SY5Y细胞共孵育可能作为体外胰岛素信号转导通路的一种细胞模型应用于某些神经药理学研究。

Objective To investigate the effect of streptozotocin （STZ） on the growth of human neuroblastoma SH-SY5Y cells and express change of correlation protein of in vitro-insulin signaling pathway. Methods Cell metabolic rate and lactate dehydrogenase （LDH） leakage rate were assessed. The expressions of insulin （Ins） receptor substrate-1 （IRS-1）, phosphatidylinositol-3-kinase （PI3K） were tested by Western blot. Results STZ cultivated with SH-SY5Y cells could prevent the growth of human neuroblastoma SH-SY5Y cells and also prevent the growth promotion function of Ins. Its depression function obviously expressed as dose-and time-dependent. LDH leakage rate increased with the concentration of STZ increasing. The expressions of IRS-1, PI3K were found decreasing by Western blot test. Conclusions STZ might damage the human neuroblastoma SH-SY5Y cells by inhibiting the activity of tyrosine kinase on the Ins receptor and blocking the Ins signal transduction. SH-SY5Y can be a new cell model in vitro-insulin signaling passway applying to the research of neuropharmacology.