隐丹参酮对IGF-1促PC12细胞存活的作用及机制探讨

目的:研究隐丹参酮对类胰岛素样生长因子-1(IGF-1)促进PC12细胞存活的影响及可能机制.方法:首先采用剥夺血清造成细胞损伤模型确定IGF-1发挥促存活作用的剂量,然后不同剂量的隐丹参酮预先作用PC12细胞,再加入IGF-1处理,MTT检测隐丹参酮对IGF-1促PC12细胞存活的影响；Western blot检测隐丹参酮对IGF-t诱导其受体(1GF-IR)磷酸化及下游信号通路磷酯酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)及细胞外信号调节激酶(ERK) 1/2的影响.结果:MTT显示隐丹参酮能剂量依赖性地阻断IGF-1的促存活作用,抑制PC12细胞的增殖；Western blot结果显示IGF-1能明显诱导其受体(IGF-1R)磷酸化,而隐丹参酮则起抑制作用,并使下游Akt及ERK1/2的磷酸化水平下调,呈明显的剂量依赖性.结论:隐丹参酮可通过抑制IGF-1R及其下游信号分子Akt和ERK1/2的磷酸化,从而抑制IGF-1的促存活功能,发挥其自身抑制细胞存活,促使细胞凋亡的作用.

Influence and Possible Mechanisms of Cryptotanshinone on the Survival of PC12 Cells Promoted by IGF-1

Objective: Study the effect of cryptotanshinone(CTS) on the survival of in PC12 cells promoted by insulin-like growth factor-1(IGF-1) and possible mechanisms. Method: The serum deprivation model was constructed to determine the dose of IGF-1 to play the survival-promoting effect, then pretreat PC12 cells with different concentrations of CTS, then treated with IGF-1 processing 24 hours, MTT assay was used to detect the effect of CTS on protective function of IGF-1.The effect of CTS and IGF-1 on the phosphorylation level of IGF-1 receptar(IGF-1R) were analyzed by Western blot and downstream targets were also detected such as protein kinase B(Akt) and extracellular signal regulated kinase(ERK). Result: After treatment with IGF-1, cell viability of PC12 cells was increased in a dose-dependent manner as same as the phosphorylation level of IGF-1R, whereas CTS attenuated the survival promoting effect of IGF-1 in PC12 cells and decreased the phosphorylated IGF-1R. Moreover, CTS attenuated the phosphorylation of Akt and ERK1/2 induced by IGF-1in a dose-dependent manner. Conclusion: These data indicate that CTS has an inhibitory effect on PC12 cells viability via down-regulate the phosphorylation of IGF-1R and downstream Akt and ERK.