山豆根素对鼻咽癌CNE-1细胞生物学行为及MAPK信号通路的影响
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篇名: 山豆根素对鼻咽癌CNE-1细胞生物学行为及MAPK信号通路的影响
TITLE: Effects of sophoranone on the biological behavior of nasopharyngeal carcinoma CNE-1 cells and MAPK signaling pathway
摘要: 目的 研究山豆根素(SOP)对鼻咽癌CNE-1细胞生物学行为及促分裂原活化的蛋白激酶(MAPK)信号通路的影响。方法将细胞分为空白组和SOP低、中、高浓度组(SOP-L组、SOP-M组、SOP-H组,25、50、100μmol/L),检测侵袭细胞数、迁移细胞数、细胞凋亡率,以及细胞中丝裂原活化蛋白激酶激酶(MEK)、胞外信号调节激酶1(ERK1)、ERK2、c-Jun氨基端激酶(JNK)mRNA表达水平和ERK、JNK、p38丝裂原激活的蛋白激酶(简称“p38”)蛋白磷酸化水平。另将细胞分为空白组、SOP高浓度组(SOP-H组,100μmol/L)、SOP高浓度联合p38抑制剂组(SOP-H+SB组,100μmol/LSOP+10μmol/LSB)和SOP高浓度联合JNK抑制剂组(SOP-H+SP组,100μmol/LSOP+10μmol/LSP),检测侵袭细胞数、细胞迁移率和细胞中JNK、p38蛋白磷酸化水平,以及基质金属蛋白酶-9(MMP-9)、增殖细胞核抗原Ki67、活化的胱天蛋白酶-3(cleaved-caspase-3)蛋白表达水平。结果与空白组比较,各浓度SOP能显著减少或降低侵袭细胞数、迁移细胞数和MEK、ERK1、ERK2(SOP-L组除外)、JNKmRNA表达水平,提高细胞凋亡率和ERK、JNK、p38蛋白的磷酸化水平(P<0.05)。与SOP-H组比较,SOP-H+SB组和SOP-H+SP组细胞中p38、JNK蛋白磷酸化水平和cleaved-caspase-3蛋白表达水平均显著降低,侵袭细胞数、细胞迁移率和MMP-9、Ki67蛋白表达水平均显著增加或升高(P<0.05)。结论SOP可抑制CNE-1细胞增殖、迁移及侵袭,并诱导其凋亡,其作用机制可能与促进MAPK信号通路相关蛋白的磷酸化有关。
ABSTRACT: OBJECTIVE To study the effects of sophoranone (SOP) on the biological behavior of nasopharyngeal carcinoma CNE-1 cells and mitogen-activated protein kinase (MAPK) signaling pathway. METHODS CNE-1 cells were divided into blank group and SOP low-, medium- and high-concentration groups (SOP-L group, SOP-M group, SOP-H group, 25, 50 and 100 μmol/L). The number of invasive cells, the number of migratory cells, and the apoptosis rate of cells were detected. The expression levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase 1 (ERK1), ERK2, and c-Jun N-terminal kinase (JNK) mRNA, as well as phosphorylation levels of ERK, JNK, and p38 mitogen-activated protein kinase (abbreviated as “p38”) proteins in cells were all detected. Additionally, cells were divided into blank group, SOP high-concentration group (SOP- H group, 100 μmol/L), SOP high-concentration combined with p38 inhibitor group (SOP-H+SB group, 100 μmol/L SOP+10 μmol/L SB), and SOP high-concentration combined with JNK inhibitor group (SOP-H+SP group, 100 μmol/L SOP+10 μmol/L SP). The number of invasive cells, cell migration rate, and the protein phosphorylation levels of JNK and p38 in cells, as well as the protein expression levels of matrix metalloproteinase-9(MMP-9), proliferating cell nuclear antigen Ki67, and cleaved-caspase-3 were measured. RESULTS Compared with the blank group, SOP for each concentration could significantly decrease the number of invasive cells, the number of migratory cells, and mRNA expressions of MEK, ERK1, ERK2 (except for the SOP-L group) and JNK, but increase the apoptosis rate of cells and phosphorylation levels of ERK, JNK, and p38 proteins (P<0.05). Compared with the SOP-H group, the protein phosphorylation levels of p38 and JNK, and the protein expression of cleaved-caspase-3 were decreased significantly in SOP-H+SB group and SOP-H+SP group, while the number of invasive cells, cell migration rate, and the protein expression levels of MMP-9 and Ki67 were all increased significantly (P<0.05). CONCLUSIONS SOP can inhibit the proliferation, migration and invasion of CNE-1 cells, and induce the apoptosis, the mechanisms of which may be associated with promoting the phosphorylation of proteins related to the MAPK signaling pathway.
期刊: 2025年第36卷第18期
作者: 姚晨;袁东杰;李征;李芳芳;卢振民
AUTHORS: YAO Chen,YUAN Dongjie,LI Zheng,LI Fangfang,LU Zhenmin
关键字: 鼻咽癌;山豆根素;促分裂原活化的蛋白激酶;增殖;凋亡
KEYWORDS: nasopharyngeal carcinoma; sophoranone; mitogen-activated protein kinase; proliferation; apoptosis
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