大黄素抑制肺癌A549细胞增殖、迁移和侵袭及对SDF1/CXCR4轴信号通路的影响
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摘要
目的探讨大黄素对人肺癌A549细胞系增殖、侵袭和迁移能力以及SDF1/CXCR4轴信号通路的影响。方法采用MTT法检测不同浓度大黄素对肺癌A549细胞系的抑制率。通过划痕实验、Transwell小室侵袭实验分别检测大黄素对A549细胞迁移及侵袭能力的影响。荧光定量PCR检测细胞中SDF1和CXCR4基因表达,Western blot法检测A549细胞内SDF1/CXCR4轴信号通路中SDF1和CXCR4等关键蛋白表达水平的变化情况。结果大黄素对肺癌A549细胞的增殖具有抑制作用,呈浓度依赖性。大黄素以浓度依赖的方式抑制A549细胞的增殖、侵袭和迁移。荧光定量PCR检测发现大黄素处理A549细胞中SDF1和CXCR4基因表达降低。Western blot结果提示大黄素可抑制SDF1/CXCR4轴信号通路的SDF1和CXCR4蛋白的表达。结论在一定浓度范围内,大黄素可抑制人非小细胞肺癌A549细胞的增殖、迁移和侵袭,下调分泌蛋白SDF1和CXCR4的表达,其机制可能与抑制SDF1/CXCR4轴信号通路中的SDF1和CXCR4蛋白有关。
Objective To investigate the effects of emodin on the proliferation,invasion and migration of human lung cancer A549 cell line and the SDF1/CXCR4 axis signaling pathway. Methods MTT assay was used to detect the inhibition rate of different concentrations of emodin on lung cancer A549 cell line. The effects of emodin on the migration and invasion of A549 cells were examined by scratch test and Transwell chamber invasion assay. The expressions of SDF1 and CXCR4 genes in the cells were detected by real-time PCR,and the expression levels of SDF1 and CXCR4 in SDF1/CXCR4 axis signaling pathway in A549 cells were detected by Western blot. Results Emodin inhibited the proliferation of A549 cells in a concentration-dependent manner. Emodin inhibits proliferation,invasion and migration of A549 cells in a concentration-dependent manner. Real-time PCR showed that the expression of SDF1 and CXCR4 genes was decreased in emodin treated A549 cells. Western blot results indicated that emodin could inhibit the expression of SDF1 and CXCR4 proteins in the SDF1/CXCR4 axis signaling pathway. Conclusion In a certain concentration range,emodin can inhibit the proliferation,migration and invasion of human non-small cell lung cancer A549 cells,and down-regulate the expression of secreted proteins SDF1 and CXCR4,which may be related to the inhibition of SDF1 and CXCR4 in the SDF1/CXCR4 axis signaling pathway.
Objective To investigate the effects of emodin on the proliferation,invasion and migration of human lung cancer A549 cell line and the SDF1/CXCR4 axis signaling pathway. Methods MTT assay was used to detect the inhibition rate of different concentrations of emodin on lung cancer A549 cell line. The effects of emodin on the migration and invasion of A549 cells were examined by scratch test and Transwell chamber invasion assay. The expressions of SDF1 and CXCR4 genes in the cells were detected by real-time PCR,and the expression levels of SDF1 and CXCR4 in SDF1/CXCR4 axis signaling pathway in A549 cells were detected by Western blot. Results Emodin inhibited the proliferation of A549 cells in a concentration-dependent manner. Emodin inhibits proliferation,invasion and migration of A549 cells in a concentration-dependent manner. Real-time PCR showed that the expression of SDF1 and CXCR4 genes was decreased in emodin treated A549 cells. Western blot results indicated that emodin could inhibit the expression of SDF1 and CXCR4 proteins in the SDF1/CXCR4 axis signaling pathway. Conclusion In a certain concentration range,emodin can inhibit the proliferation,migration and invasion of human non-small cell lung cancer A549 cells,and down-regulate the expression of secreted proteins SDF1 and CXCR4,which may be related to the inhibition of SDF1 and CXCR4 in the SDF1/CXCR4 axis signaling pathway.
引文
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[3]陈辰,李利亚.小细胞肺癌靶向药物治疗研究进展[J].中日友好医院学报,2018,32(2):111-114.
[4]钱芳芳,罗斌,阙祖俊,等.中医药调控免疫功能防治肺癌的研究进展[J].辽宁中医杂志,2018,33(5):1098-1102.
[5]董福光,邓彦,马明越,等.中草药抗肺癌细胞的分子机制[J].中华中医药杂志,2015,23(4):1188-1190.
[6]王婷婷,周海燕,王亚贤,等.中药多糖抗肺癌作用研究进展[J].中医药学报,2016,44(2):92-95.
[7] Barbieri F,Bajetto A,Porcile C,et al. Role of stromal cell-derived factor 1(SDF1/CXCL12)in regulating anterior pituitary function[J]. J Mol Endocrinol,2007,38(3):383-389.
[8] Wu T,Yang L,Chen Y,et al. Pilose antler polypeptides ameliorates hypoxic-ischemic encephalopathy by activated neurotrophic factors and SDF1/CXCR4 axis in rats[J]. Acta Biochimica et Biophysica Sinica,2018,50(3):254-262.
[9]陈万青,郑荣寿,张思维,等. 2013年中国恶性肿瘤发病和死亡分析[J].中国肿瘤,2017,29(1):1-7.
[10]王松,陶毅明.芦荟大黄素抗肿瘤作用的研究进展[J].华夏医学,2017,30(3):160-163.
[11]魏泽英,虎春艳,李树全.蒽醌类似物的合成及其生物活性研究进展[J].中国药房,2015,41(25):3581-3583.
[12]郑言博,马卓.蒽醌类化合物抗菌与抗肿瘤活性的研究进展[J].湖北中医杂志,2012,34(2):74-76.
[13]孙桂斌,张萌,严方,等.大黄素抗肿瘤活性及相关机制研究进展[J].药学进展,2013,23(6):248-256.
[14]Yang F,Sun W,Luo W,et al. SDF1-CXCR4 signaling contributes to the transition from acute to chronic pain state[J]. Mol Neurobiol,2017,54(4):2763-2775.
[15]李红玉,陈科达,于海涛,等. CXCL12(SDF-1)/CXCR4信号传导通路及其肿瘤相关性研究进展[J].中国小儿血液与肿瘤杂志. 2011,16(6):279-282.
[16]韦秋业,邹崇祺. CXCL12/CXCR4信号通路对肿瘤的作用及机制的研究进展[J].现代肿瘤医学.2017,25(20):3361-3364.
[17]吴洋,李东云,张巍琼,等.益肾养阴合剂通过CXCR4/STAT3信号通路对MRL/lpr小鼠肾脏发挥保护作用[J].中国实验方剂学杂志. 2018,36(9):127-133.
[18]朱华琦. FK506促肝癌复发转移的研究及CXCR4/SDF1α的相关性改变[D].复旦大学,2009.
[19]DvoránkováB,Szabo P,Kodet O,et al. Intercellular crosstalk in human malignant melanoma[J]. Protoplasma,2016,23(9):1-8.
[20]于正洪,王苏莉,史兆荣,等.老年人恶性肿瘤研究进展[J].现代肿瘤医学,2009,17(7):1357-1359.
[21]李敏,谢明.多原发恶性肿瘤研究进展[J].中国癌症杂志,2017,27(2):156-160.
[22]金松,田立华,苏勤,等. IL-24可能通过CXCL12/CXCR4信号轴抑制口腔鳞癌细胞迁移及侵袭能力[J].口腔医学研究,2017(5):482-485.