川芎嗪对宫颈癌细胞增殖和侵袭转移的抑制作用及分子机制

Inhibitory Effect and Molecular Mechanism of Ligustrazine on Proliferation,Invasion and Metastasis of Cervical Cancer Cells

目的探究川芎嗪(TMP)对人宫颈癌细胞增殖、侵袭和迁移的影响及其机制。方法用含有质量浓度为0、0.25、0.50、1.00和2.00 mg·mL^(-1) TMP的培养基处理人宫颈癌SiHa细胞后,用CCK-8法检测细胞增殖能力;用Transwell小室检测细胞侵袭、迁移能力;用蛋白免疫印记法检测细胞内上皮-间质转化(EMT)相关蛋白、基质金属蛋白酶2/7/9(MMP2/7/9)和PI3K/AKT/GSK-3β通路相关蛋白的表达水平。结果在0.25~2.00 mg·mL^(-1)浓度范围内,TMP对SiHa细胞的增殖、侵袭和迁移表现出浓度依赖性的抑制作用(P<0.05或P<0.01);与0 mg·mL^(-1) TMP处理组相比,0.50、1.00和2.00 mg·mL^(-1) TMP处理组细胞内E-Cadherin、PI3K、p-AKT及p-GSK-3β表达水平显著上升,而N-cadherin、Vimentin、β-Catenin和MMP2/7/9的表达水平显著下降(P<0.05或P<0.01)。结论TMP可能通过激活PI3K/AKT/GSK-3β信号通路抑制EMT过程和MMPs表达,抑制人宫颈癌SiHa细胞增殖、侵袭和转移。

Objective To observe the effects of ligustrazine(TMP)on the proliferation,invasion and migration of human cervical cancer cells and its mechanism of action.Methods Human cervical cancer SiHa cells were treated with different concentrations of TMP(0,0.25,0.50,1.00 and 2.00 mg·mL^(-1)).The proliferative capacity of cells was detected by CCK-8 assay.The migratory and invasive abilities of cells were analyzed by Transwell assay.Epithelial-mesenchymal transition(EMT)-related proteins,matrix metalloproteinase(MMP)-2/-7/-9,and PI3K/AKT/GSK-3βpathway-associated proteins were determined by Western blot.Results Treatment with TMP(0.25-2.00 mg·mL^(-1))inhibited the proliferation,invasion and migration of SiHa cells in a concentration-dependent manner(P<0.05 or P<0.01).Furthermore,TMP treatment at doses of 0.50,1.00 and 2.00 mg·mL^(-1) up-regulated the expression of E-cadherin,PI3K,p-AKT and p-GSK-3β,and down-regulated the expression of N-cadherin,Vimentin,β-catenin and MMP2/7/9 in SiHa cells(P<0.05 or P<0.01).Conclusion TMP may suppress EMT and MMP expression by activating PI3K/AKT/GSK-3βsignaling pathway,and ultimately inhibit the proliferation,invasion and metastasis of human cervical cancer SiHa cells.