Liao Hehe, Wang Zhouquan, Deng Zhiping, Ren Hong, Li Xiaojun
Second Department of Throcic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University 277 West Yanta Road, Xi'an, Shaanxi 710061, China ; Department of Oncology, The 215 Hospital of Nuclear Industry 35 West Weiyang Road, Xianyang, Shaanxi 712000, China.
Department of Oncology, Shannxi Sengong Hospital 9 Huanzhan Street of Huxian, Xi'an, Shaanxi 710300, China.
Int J Clin Exp Med. 2015 Jun 15;8(6):8948-57. eCollection 2015.
Glucose transporter (GLUT) 1 is found highly expressed in malignant tumors and considered a mediator inducing cancer metastasis. Curcumin is a natural product which exerts anti-invasion and metastasis effects in cancer. This study aimed at evaluating whether attenuating GLUT1 was involved in curcumin's anti-invasion and metastasis effects. In the in vitro part, constricted pcDNA3.1-GLUT1 vector was transfected into A549 cells. MTT assay was used to assess the curcumin's effects on proliferation in lung cancer A549 cells. Transwell assay was used to evaluate the anti-invasion effect of curcumin on A549 cells. Real-time PCR and Western-blotting were employed to examine the expression levels of GLUT1, membrane type 1-MMP (MT1-MMP) and matrix metalloproteinase (MMP) 2 in curcumin- incubated A549 cells. In the in vivo part, tumor weight and metastatic rate were assessed in nude mice bearing untransfected, empty vector transfected and pcDNA3.1-GLUT1 transfected A549 cells originated tumors. In this study, we found that curcumin began to show significant cytotoxicity against proliferation effect at 45 μmol/L. Curcumin inhibited invasion and expressions of GLUT1, MT1-MMP and MMP2 untransfected A549 cells in a concentration-dependent manner. pcDNA3.1-GLUT1 transfected A549 cells exhibited resistance to curcumin's anti-invasion effect by up-regulating expressions of GLUT2, MT1-MMP and MMP2. Furthermore, curcumin failed to decrease the metastatic rate in nude mice bearing pcDNA3.1-GLUT1 transfected A549 cells originated tumors. These results suggested that curcumin inhibit lung cancer invasion and metastasis by attenuating GLUT1/MT1-MMP/MMP2 pathway.
葡萄糖转运蛋白（GLUT）1在恶性肿瘤中高表达，被认为是诱导癌症转移的介质。姜黄素是一种天然产物，对癌症具有抗侵袭和转移作用。本研究旨在评估GLUT1的下调是否参与姜黄素的抗侵袭和转移作用。在体外实验部分，将构建的pcDNA3.1-GLUT1载体转染至A549细胞。采用MTT法评估姜黄素对肺癌A549细胞增殖的影响。采用Transwell法评估姜黄素对A549细胞的抗侵袭作用。采用实时定量PCR和蛋白质印迹法检测姜黄素作用后的A549细胞中GLUT1、膜型基质金属蛋白酶1（MT1-MMP）和基质金属蛋白酶（MMP）2的表达水平。在体内实验部分，评估接种未转染、空载体转染及pcDNA3.1-GLUT1转染的A549细胞来源肿瘤的裸鼠的肿瘤重量和转移率。在本研究中，我们发现姜黄素在45μmol/L时开始对增殖效应显示出显著的细胞毒性。姜黄素以浓度依赖的方式抑制未转染的A549细胞的侵袭以及GLUT1、MT1-MMP和MMP2的表达。pcDNA3.1-GLUT1转染的A549细胞通过上调GLUT2、MT1-MMP和MMP2的表达而对姜黄素的抗侵袭作用产生抗性。此外，姜黄素未能降低接种pcDNA3.1-GLUT1转染的A549细胞来源肿瘤的裸鼠的转移率。这些结果表明，姜黄素通过减弱GLUT1/MT1-MMP/MMP2信号通路来抑制肺癌的侵袭和转移。
