异甘草素对人骨肉瘤细胞MG-63增殖及侵袭的影响
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摘要
目的探讨异甘草素(ISL)对人骨肉瘤细胞MG-63增殖及侵袭的影响及可能机制。方法采用不同浓度异甘草素(0,5,10,20μg/ml)作用于MG-63细胞后,四甲基偶氮唑蓝(MTT)比色法观察ISL对MG-63细胞生长的抑制作用。单一浓度的异甘草素(20μg/ml)处理MG-63细胞48h后,Transwell实验检测MG-63细胞侵袭能力变化,Western blot方法检测Bcl-2、Bax及自噬相关蛋白Beclin1、LC3的表达,实时PCR方法检测Bcl-2mRNA与Bax mRNA的表达水平。结果 ISL以浓度依赖性抑制MG-63细胞增殖。经20μg/ml异甘草素处理后,MG-63细胞侵袭能力显著降低,Bcl-2蛋白的表达下调,Bax及自噬相关蛋白Beclin1、LC3蛋白的表达上调,Bcl-2 mRNA的表达水平下调,Bax mRNA的表达水平上调。结论异甘草素在体外能够抑制MG-63细胞增殖与侵袭,与激活线粒体凋亡通路及自噬通路相关。
Objective To investigate the effect of isoliquiritigenin(ISL) on the proliferation and invasion of human osteosarcoma cell line MG-63 and its possible mechanism. Methods The effects of ISL on MG-63 cells proliferation was observed by methyl thiazolyl tetrazolium(MTT) after different concentrations of ISL(0,5,10,20 ug/ml) was treated. 48 later, treatment with a single concentration of isoglycyrrhizin(μg/ml), the invasive ability of MG-63 cells was detected by Transwell assay, the expressions of Bcl-2, Bax, autophagy-related proteins Beclin1 and LC3 were detected by Western blot, and the expressions of Bcl-2 mRNA and Bax mRNA were detected by real-time PCR. Results ISL inhibited the proliferation of MG-63 cells in a concentration dependent manner. After treatment with 20 μg/ml ISL, the invasive ability of MG-63 cells was significantly decreased, and the expression level of Bcl-2 protein and m RNA was downregulated, the expression level of Bax protein and mRNA, and autophagy-related proteins Beclin1 and LC3 were upregulated. Conclusion ISL inhibited the proliferation and invasion of MG-63 cells in vitro, which was related to the activation of mitochondrial apoptosis pathway and autophagy pathway.
Objective To investigate the effect of isoliquiritigenin(ISL) on the proliferation and invasion of human osteosarcoma cell line MG-63 and its possible mechanism. Methods The effects of ISL on MG-63 cells proliferation was observed by methyl thiazolyl tetrazolium(MTT) after different concentrations of ISL(0,5,10,20 ug/ml) was treated. 48 later, treatment with a single concentration of isoglycyrrhizin(μg/ml), the invasive ability of MG-63 cells was detected by Transwell assay, the expressions of Bcl-2, Bax, autophagy-related proteins Beclin1 and LC3 were detected by Western blot, and the expressions of Bcl-2 mRNA and Bax mRNA were detected by real-time PCR. Results ISL inhibited the proliferation of MG-63 cells in a concentration dependent manner. After treatment with 20 μg/ml ISL, the invasive ability of MG-63 cells was significantly decreased, and the expression level of Bcl-2 protein and m RNA was downregulated, the expression level of Bax protein and mRNA, and autophagy-related proteins Beclin1 and LC3 were upregulated. Conclusion ISL inhibited the proliferation and invasion of MG-63 cells in vitro, which was related to the activation of mitochondrial apoptosis pathway and autophagy pathway.
引文
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[11]Zheng H,Li Y,Wang Y,et al.Downregulation of COX-2 and CYP4Asignaling by isoliquiritigenin inhibits human breast cancer metastasisthrough preventing anoikis resistance,migration and invasion[J].Toxicol Appl Pharmacol,2014,280(1):10-20.
[12]Kang SW,Choi JS,Choi YJ,et al.Licorice isoliquiritigenin dampensangiogenic activity via inhibition of MAPK-responsive signalingpathways leading to induction of matrix metalloproteinases[J].J Nutr Biochem,2010,21(1):55-65.
[13]Kang SW,Choi JS,Choi JY,et al.Licorice isoliquiritigenin dampensangiogenic activity via inhibition of MAPK-responsive signalingpathways leading to induction of matrix metalloproteinases[J].J Nutr Biochem,2010,21(1):55-65.
[2]Inbar feigenberg M,Choufani S,Butcher DT,et a1.Basic concepts of epigenetics[J].Fertil Steril,2013,99(3):607-615.
[3]Ablise M,Wang Y B,Xu FY,et al.Anticancer property ofisoliquiritigenin and 3-oximethyl-isoliquiritigenin in human Bel-7402hep-atoma cell lines[J].Chin Pharmacol Bull,2014,30(6):887-888.
[4]Zhang X,Zhu P,Zhang X,et al.Natural antioxidantisoliquiritigeninameliorates contractile dysfunction of hypoxic cardiomyocytes viaAMPK signaling pathway[J].Mediators Inflamm,2013,2013:390890-390895.
[5]Hirchaud F,Hermetet F,Ablise M,et al.Isoliquiritigen inducescaspase-dependent apoptosis via down regulation of HPV16E6 expressionin cervical cancer ca ski cells[J].Planta Med,2013,79(17):1628-1635.
[6]戴颖,王强.miR-124靶向Sp1对人骨肉瘤MG-63细胞增殖的调控[J].解剖科学进展,2017,23(2):167-170.
[7]陈亚斌,陈宇,顾淑贤.沉默HAX1基因对人骨肉瘤细胞凋亡的影响[J].解剖科学进展,2018,24(4):401-403.
[8]Cuendet M,Guo J,Luo Y,et al.Cancer chemopreventive activity and metabolism of isoliquiritigenin,a compound found in licorice[J].Cancer Prev Res,2010,3(2):221-232.
[9]Li Y,Zhao H,Wang Y,et al.Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidouic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer[J].Toxicol Appl Pharmacol,2013,272(1):37-48.
[10]Wu S,Xue J,Yang Y,et al.Isoliquiritigenin inhibits interferon-γinducible genes expression in hepatocytes through downregulatingactivation of JAK1/STAT1,IRF3/MyD88,ERK/MAPK,JNK/MAPK and PI3K/Akt signaling pathways[J].Cell Physiol Biochem,2015,37(2):501-514.
[11]Zheng H,Li Y,Wang Y,et al.Downregulation of COX-2 and CYP4Asignaling by isoliquiritigenin inhibits human breast cancer metastasisthrough preventing anoikis resistance,migration and invasion[J].Toxicol Appl Pharmacol,2014,280(1):10-20.
[12]Kang SW,Choi JS,Choi YJ,et al.Licorice isoliquiritigenin dampensangiogenic activity via inhibition of MAPK-responsive signalingpathways leading to induction of matrix metalloproteinases[J].J Nutr Biochem,2010,21(1):55-65.
[13]Kang SW,Choi JS,Choi JY,et al.Licorice isoliquiritigenin dampensangiogenic activity via inhibition of MAPK-responsive signalingpathways leading to induction of matrix metalloproteinases[J].J Nutr Biochem,2010,21(1):55-65.