SRPK1激活PI3K/AKT通路对三阴性乳腺癌细胞恶性进展的影响

Effect of SRPK1 on Malignant Progression of Triple Negative Breast Cancer Cells by Activation of the PI3K/AKT Pathway

目的探索SRPK1与PI3K/AKT途径在三阴性乳腺癌恶性进展中的作用。方法免疫组化实验检测三阴性乳腺癌组织以及癌旁组织SRPK1的表达水平;将三阴性乳腺癌细胞系MDA-MB-231细胞分为3个实验组:siSRPK1组、siNC组以及LY294002组。通过MTT实验检测MDA-MB-231细胞的增殖能力;通过Transwell实验分析MDA-MB-231细胞的侵袭能力;通过流式细胞术分析MDA-MB-231细胞的凋亡率;通过蛋白免疫印迹检测PI3K/AKT信号通路以及SRPK1蛋白的表达水平。结果和三阴性乳腺癌的癌旁组织比较,三阴性乳腺癌组织SRPK1的表达水平增加。与siNC组比较,siSRPK1以及LY294002组的MDA-MB-231细胞增殖能力下降(P<0.05);siSRPK1以及LY294002组的MDA-MB-231细胞侵袭数减少(P<0.05);siSRPK1以及LY294002组的MDA-MB-231细胞凋亡率升高(P<0.05);siSRPK1以及LY294002组的MDAMB-231细胞PI3K、AKT蛋白水平降低(P<0.05)。结论SRPK1在三阴性乳腺癌组织中高表达,抑制SRPK1表达后,三阴性乳腺癌MDA-MB-231细胞的增殖以及侵袭能力降低,凋亡率增加,这一过程与SRPK1调控PI3K/AKT通路相关。

Objective To explore the role of SRPK1 and PI3K/AKT signaling pathway in the malignant progression of triple negative breast cancer(TNBC)cells.Methods The expression level of SRPK1 in TNBC tissues and adjacent tissues was detected by immunohistochemistry.TNBC cell line MDA-MB-231 cells were divided into three groups:siSRPK1 group,siNC group and LY294002 group.The proliferation ability of MDA-MB-231 cells was detected by MTT assay.Transwell assay was used to analyze the invasion ability of MDA-MB-231 cells.The apoptosis rate of MDA-MB-231 cells was analyzed by flow cytometry.The expression of PI3K/AKT signaling pathway related proteins and SRPK1 protein were detected by Western blotting.Results The expression level of SRPK1 was increased in the TNBC tissues when compared with that in the adjacent tissues.The growth rates of MDA-MB-231 cells in the siSRPK1 and LY294002 groups were decreased when compared with that in the siNC group(P<0.05).The numbers of invasive MDA-MB-231 cells in the siSRPK1 and LY294002 groups were significantly decreased(P<0.05).The apoptosis rates of MDA-MB-231 cells in the siSRPK1 and LY294002 groups were significantly increased(P<0.05).The protein expression levels of PI3K and AKT in MDA-MB-231 cells were significantly decreased in the siSRPK1 and LY294002 groups(P<0.05).Conclusion SRPK1 is highly expressed in TNBC tissues.After inhibiting the expression of SRPK1,the proliferation and invasion ability of TNBC MDA-MB-231 cells are decreased,and the apoptosis rate is increased.This process is related to the regulation of SRPK1 on PI3K/AKT pathway.