白花丹素对舌鳞状细胞癌细胞的侵袭和迁移的作用及机制研究

Effect of Plumbaginon on Invasion and Migration of Tongue Squamous Cell Carcinoma Cells and Its Mechanism

目的:探讨葡萄糖转运蛋白1(glucose transporter isoform 1,GLUT1)与舌鳞状细胞癌(tongue squamous cell carcinoma,TSCC)转移的关系,以及白花丹素(plumbagin,PLB)对TSCC细胞侵袭和迁移的影响及作用机制。方法:免疫组化分析GLUT1和基质金属蛋白酶2(matrix metalloprotein 2,MMP2)与TSCC转移的关系。MTT检测PLB对TSCC细胞的增殖抑制作用,并计算24h的IC50值。Transwell、划痕实验和Westernblot分别检测肿瘤细胞的侵袭和迁移能力以及相关蛋白的表达改变。结果:免疫组化显示GLUT1和MMP2的高表达与TSCC的转移密切相关(P<0.05)。MTT显示PLB作用24h的IC50值为6.87μmol/L;Transwell以及划痕实验分别显示,PLB及NSC207895、WZB117处理组的细胞穿膜数及迁移率明显减少(P<0.05);Westernblot显示,PLB处理后p53表达升高(P<0.05)、GLUT1以及MMP2表达下降(P<0.05);NSC207895处理后GLUT1及MMP2表达下降(P<0.05);WZB117处理后p53无明显改变(P>0.05)、MMP2表达下降(P<0.05)。结论:GLUT1高表达与TSCC转移密切相关,PLB可通过调控p53/GLUT1/MMP2通路抑制TSCC细胞的侵袭和迁移。

Objective：To investigate the relationship between Glucose transporter isoform 1（GLUT1）and metastasis of tongue squamous cell carcinoma（TSCC）and the effect and mechanism of plumbagin（PLB）on the invasion and migration of TSCC cells.Methods：The relationship between metastasis of TSCC and GLUT1 or Matrix metalloprotein 2（MMP2）was detected by immunohistochemical assay.The proliferation inhibition effect and the half inhibitory concentration（IC50）of plumbagin on TSCC cells were detected by MTT assay.The invasion ability and migration ability were detected by Transwell assay and wound healing test,respectively.And the expressions of p53,GLUT1,and MMP2 were evaluated by Western blot.Results：The high expression of GLUT1 and MMP2 was closely related to the metastasis of TSCC（P〈0.05）.MTT assay showed that the IC50 of PLB to TSCC cells for24 hwas 6.78μmol/L.Transwell assay and wound healing test showed that PLB and NSC207895 and WZB117 significantly reduced the number of transmembrane cells and cell mobility.Western blot showed that the expression of p53 increased,while the expression of GLUT1 and MMP2 decreased after treatment of PLB（P〈0.05）.The expression of GLUT1 and MMP2 decreased（P〈0.05）after treatment of NSC207895.And the expression of MMP2 decreased（P〈0.05）after treatment of WZB117.However,the expression of p53 was not changed（P〈0.05）.Conclusion：The high expression of GLUT1 is closely related to the metastasis of TSCC.Plumbagin can inhibit the invasion and migration of TSCC through p53/GLUT1/MMP2 pathway.