萝卜硫素通过ANXA3/p38和JNK信号通路诱导人皮肤鳞状细胞癌细胞凋亡

Sulforaphane Induces the Apoptosis of Human Skin Squamous Cell Carcinoma Cells through ANXA3/p38 and JNK Signaling Pathways

目的研究萝卜硫素(SFP)对人皮肤鳞状细胞癌(sSCC)A431细胞生长影响的分子机制。方法CCK8法和流式细胞术分析A431细胞活力及凋亡相关指标;蛋白质印迹法(WB)检测A431细胞中凋亡相关蛋白、膜联蛋白A3(ANXA3)、磷酸化-p38(p-p38)和磷酸化应激活化蛋白激酶(p-JNK)水平。结果SFP抑制A431细胞活力、细胞周期进展及增殖;SFP还诱导A431细胞中Caspase-3/9活性上调及细胞凋亡;SFP抑制A431细胞中ANXA3/p38和JNK信号通路活化;然而,p38激动剂HY-N0168和JNK激动剂MPT0B392能部分逆转SFP对A431细胞的毒性作用;SFP通过ANXA3降低p38和JNK信号通路活化及A431细胞的毒性作用。结论SFP可通过抑制ANXA3/p38和JNK信号通路诱导A431细胞的凋亡。

Objective In order to study the molecular mechanism in the effects of sulforaphane(SFP)on the proliferation and apoptosis of human skin squamous cell carcinoma(sSCC)A431 cells.Methods The effects of SFP on the cell viability,proliferation and apoptosis were respectively measured by using Cell Counting Kit-8(CCK-8)assay and flow cytometry assay.Western blotting was used to investigate the impacts of SFP on the expression levels of apoptotic proteins,Annexin A3(ANXA3),p-p38 and phosphorylated c-JunN-terminal kinase(p-JNK)inA431 cells.Results SFP dose-dependently inhibited the survival,cell cycle progression and proliferation of A431 cells.SFP induced Caspase-3/9 and apoptosis activation in A431 cells.SFP suppressed the activation of ANXA3/p38 and JNK pathways in A431 cells.Conversely,its cytotoxicity against A431 cells was largely attenuated by cotreatment of p38 activator hesperetin(HY-N0168)the c-Jun N-terminal kinase(JNK)activator MPT0B392.SFP decreased the activation of p38 and JNK cascades and the cytotoxicity against A431 cells through ANXA3.Conclusion SFP could induce the apoptosis of sSCC cells via inhibiting the activation of ANXA3/p38 and JNK pathways.