木犀草素对人结直肠癌干细胞样细胞转移能力的影响及机制
摘要
目的 观察木犀草素对人结直肠癌干细胞样细胞(CSCLC)转移能力的影响,并探讨其机制。方法 将结直肠癌LoVo细胞置于含有多种细胞因子的无血清DMEM/F12培养基中培养出肿瘤细胞微球,采用流式细胞术检测LoVo细胞及其来源的CSCLC表面标志物CD44~+和CD133~+表达率。木犀草素作用CSCLC后,采用CCK-8细胞增殖实验、Transwell侵袭实验等检测CSCLC增殖能力和侵袭能力;Western blot检测E-cadherin、Twist、TCF-4、β-catenin和MMP-2蛋白表达量。结果 LoVo细胞在干细胞培养环境中可培养出肿瘤细胞微球,连续传代能形成新的微球;来源于LoVo细胞的CSCLC表面CD44~+或CD133~+表达率明显高于LoVo细胞(P<0.05)。木犀草素能有效抑制CSCLC的增殖,呈现剂量依赖性;Transwell迁移实验证实木犀草素抑制CSCLC的侵袭能力随着浓度的增加而增强;Western blot证实木犀草素上调E-cadherin蛋白表达量,下调Twist、β-catenin、TCF-4和MMP-2蛋白表达量。结论 木犀草素显著抑制结直肠癌LoVo细胞来源的CSCLC侵袭和转移能力,其作用机制可能是通过抑制Wnt/β-catenin/TCF-4信号通路来实现的。
引文
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[4] Zang MD,Hu L,Fan ZY,et a1.Luteolin suppresses gastric cancer progression by reversing epithelial- mesenchymal transition via suppression of the notch signaling pathway[J].J Transl Med,2017,15(1):52.
[5] Chen Z,Zhang B,Gao F,et al.Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts[J].Oncol Lett,2018,15(2):1559.
[6] Guo PT,Wang JC,Gao WC,et al.Salvianolic acid B reverses multidrug resistance in nude mice bearing human colon cancer stem cells[J].Mol Med Rep,2018,18:1323.
[7] Fukuda T,Oda K,Wada-Hiraike O,et a1.The anti-malarial chloroquine suppresses proliferation and overcomes cisplatin resistance of endometrial cancer cells via autophagy inhibition[J].Gynecol Oncol,2015,137(3):538.
[8] Cherciu I,Barbalan A,Pirici D,et al.Stem cells,colorectal cancer and cancer stem cell markers correlations[J].Curr Health Sci J,2014,40(3):153.
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[12] Teng L,Peng S,Guo H,et al.Conditioned media from human ovarian cancer endothelial progenitor cells induces ovarian cancer cell migration by activating epithelial-to-mesenchymal transition[J].Cancer Gene Ther,2015,22(11):518.
[13] Chen Z,Zhu Y,Dong Y,et al.Overexpression of TrpC5 promotes tumor metastasis via the HIF-1α/Twist signaling pathway in colon cancer[J].Clin Sci,2017,131(19):2439.
[14] Wang D,Rai B,Qi F,et al.Influence of the Twist gene on the invasion and metastasis of colon cancer[J].Oncol Rep,2018,39(1):31.
[15] Huber AH,Weis WI.The structure of the β-catenin/e-cadherin complex and the molecular basis of diverse ligand recognition by β-catenin.Cell,2001,105(3):391.
[16] Zhao Y,Yu T,Zhang N,et al.Nuclear E-cadherin acetylation promotes colorectal tumorigenesis via enhancing β-catenin activity[J].Mol Can Res,2019,17(2):655.
[17] Hsu HH,Kuo WW,Day CH,et al.Taiwanin E inhibits cell migration in human LoVo colon cancer cells by suppressing MMP-2/9 expression via p38 MAPK pathway[J].Environ Toxicol,2017,32(8):2021.
[18] Li C,Lu S,Wang Y,et al.Influence of micro RNA-34a on proliferation,invasion and metastasis of HCT116 cells[J].Mol Med Rep,2017,15(2):833.