苦参碱通过P38通路调节H2AX磷酸化抑制宫颈癌细胞的增殖及迁移  

Matrine inhibits proliferation and migration of cervical cancer cells through H2AX phosphorylation regulated by P38 signaling pathway

作　　者：赵淑婷 雷蕾[1] 程静新[1] ZHAO Shu.ting;LEI Lei;CHENG Jing.xin(Dept.of Obstetrics and Gynecology,East Hospital,Tongji University,Shanghai 200120,China)

机构地区：[1]同济大学附属东方医院妇产科,上海200120

出　　处：《同济大学学报（医学版）》2018年第4期22-28,共7页Journal of Tongji University(Medical Science)

基　　金：国家自然科学基金(81360380)

摘　　要：目的探讨苦参碱对宫颈癌细胞增殖、凋亡、迁移的影响及其可能的分子机制。方法不同浓度苦参碱作用于宫颈癌细胞,通过CCK8法,Ed U法、流式细胞术、Transwell实验、划痕实验检测细胞的增殖、凋亡、迁移能力。利用Western印迹法检测苦参碱对H2AX磷酸化蛋白(即γH2AX)、P38磷酸化蛋白(即p P38)水平的影响。通过干扰H2AX(Ser139)位点的磷酸化,检测苦参碱对宫颈癌细胞增殖、迁移的影响。通过干扰P38磷酸化,检测苦参碱对H2AX磷酸化的影响。结果苦参碱对宫颈癌细胞体外增殖具有显著抑制作用(P<0.05),且呈药物浓度依赖性;苦参碱显著提高细胞凋亡率,而对迁移能力具有显著抑制作用(P<0.05);苦参碱能够显著促进γH2AX及p P38蛋白的表达(P<0.05),且呈浓度依赖性。H2AX(Ser139)位点的磷酸化是苦参碱发挥抑增殖和迁移的作用位点。苦参碱通过P38通路调控H2AX(Ser139)位点的磷酸化。结论苦参碱抑制宫颈癌细胞的增殖和迁移,诱导细胞凋亡,可能是通过调控P38通路使H2AX(Ser139)位点磷酸化发挥对宫颈癌的抑癌作用。Objective To investigate the effects of matrine on the proliferation and migration ofcervical cancer cells and the underlying mechanisms. Methods CCK.8 assay, EdU assay, Transwellassay and wound.healing assay were applied to examine the proliferation, apoptosis and migration ofcervical cancer SiHa and C33A cells. Western blotting was applied to detect the expression of H2AXand P38 in cervical cancer cells. CCK8 and Transwell assay were used to detect the effect of matrine onthe cell proliferation and migration by interfering with H2AX phosphorylation. Western blot was used todetect the H2AX phosphorylation by interfering with P38 phosphorylation. Results Matrinesuppressed the proliferation（P〈0. 05）, induced apoptosis and inhibited the migration of cervical cancercells（P〈0. 05）. Further investigation discovered that matrine significantly induced the phosphorylationof the H2AX and P38 in a dose.dependent manner （ P 〈 0. 05）. Matrine inhibited proliferation andmigration by phosphorylation of H2AX （ Ser139） site. Matrine regulated phosphorylation of H2AX （Ser139 ） site through the P38 pathway. Conclusion Matrine can inhibit cervical cancer cellproliferation and migration in vitro and this action may be related to P38 signaling pathway andphosphorylation of H2AX （Ser139） site.

关 键 词：苦参碱 宫颈癌 增殖 P38 H2AX基因 

分 类 号：R711[医药卫生—妇产科学]