STAT3信号转导通路调控人宫颈癌Hela细胞增殖、凋亡的机制

Mechanism of STAT3 signal transduction pathway in regulation of proliferation and apoptosis of human cervical cancer Hela cells

目的:探讨信号传导和转录激活因子3(Stat3)通路与人宫颈癌Hela细胞增殖、凋亡的关系,明确以Stat3为靶向的信号传导通路调控Hela细胞增殖、凋亡的分子机制。方法:人宫颈癌Hela细胞用酪氨酸激酶(JAK)抑制剂AG490处理,采用噻唑蓝(MTT)比色法检测细胞增殖;流式细胞仪(FCM)测细胞凋亡及细胞周期;蛋白免疫印迹法(Western blot)检测JAK2、Stat3、磷酸化Stat3(p-Stat3)、CyclinD1、Survivin的表达。结果:人宫颈癌Hela细胞中Stat3、p-Stat3、JAK2呈阳性表达。AG490呈时间和剂量依赖的方式抑制Hela细胞的增殖,促进其凋亡(P<0.05)。Western blot检测显示p-Stat3、CyclinD1、Survivin的表达水平随作用剂量的增大而逐渐下降(P<0.05),Stat3的表达未见明显变化(P≥0.05)。结论:Stat3信号转导通路与宫颈癌Hela细胞的增殖、凋亡密切相关,可能通过其下游靶基因蛋白CyclinD1、Survivin发挥作用。阻断Stat3信号通路可能为宫颈癌的防治提供一种新的策略。

Objective ： To explore the relationship between signal transducer and activator of transcription 3 （ STAT3 ） pathway and proliferation and apoptosis of human cervical cancer Hela cells, analyze the molecular mechanism of STAT3 signal transduction pathway in regulation of proliferation and apoptosis of human cervical cancer Hela cells. Methods： Human cervical cancer Hela cells were treated with AG490 （a tyrosine kinase inhibitor） , MTT assay was used to detect cell proliferation; flow eytometry was used to detect apoptosis and cell cycle; Western blot was used to detect the expressions of tyrosine kinase 2, STAT3, phosphorylated STAT3, CyelinD1 and Survivin. Results： STAT3, phosphorylated STAT3 and tyrosine kinase 2 expressed in human cervical cancer Hela ceils. AG490 inhibited the proliferation and promoted the apoptosis of Hela cells by a time and dose dependent manner （ P 〈 0. 05 ） . Western blot detection showed that the expression levels of phosphorylated STAT3, CyelinD1 and Survivin decreased gradually with the increase of dose （P 〈 O. 05 ） , the expression of STAT3 didnl change （P≥0.05 ） . Conclusion： STAT3 signal transduction pathway is related to proliferation and apoptosis of human cervical cancer Hela cells closely, which may play a role through downstream target gene proteins （CyclinD1 and Survivin ） . Blocking STAT3 signal transduction pathway may become a new strategy to prevent and treat cervical cancer.