Curcumin Inhibits Lung Cancer Invasion and Metastasis by Attenuating GLUT1/MT1-MMP/MMP2 Pathway

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.