| Curcumin is a natural phytochemical with excellent research value. So far, many studieshave confirmed that curcumin can affect various steps of tumor occurrence, development andmetastasis. However the molecular biology mechanism of its anti-cancer effects is complex,and still unclear. This paper mainly studies the effect of curcumin in thyroid cancer onapoptotic, metastatic and the related mechanism. This study is designed to provide thetheoretical basis of curcumin on the prevention and treatment of thyroid cancer.Firstly, we studied the effects of curcumin on cell growth and metastasis process in threedifferent types of thyroid cancer. It was found that12.5-100μmol/L of curcumin had differentdegrees of inhibition of cell growth, attachment and migration of papillary thyroid cancer K1,follicular thyroid cancer133and undifferentiated thyroid cancer8505C. In addition,50and100μmol/L of curcumin could inactive matrix metalloproteinase-9(MMP-9) that was a kindof metastasis-associated enzymes in K1cells, while the same concentration of curcumindidn’t affect the activity of MMP-9in133and8505C cells. Therefore, we selected papillarycancer cells as research subject in further experiments.We used type I collagen, poly-L-lysine and concanavalin A as bases to study the impactof curcumin on cell spreading which was the following step after attachment. We found12.5-50mol/L of curcumin inhibited cell spreading on collagen and concanavalin A in K1. Invitro invasion, migration assay and wound healing assay, we found12.5-50μmol/L ofcurcumin could significantly inhibit cell migration and invasion. By gelatin zymography,Western blot and RT-PCR, we found50μmol/L of curcumin completely inhibited thesecretion and activity of MMP-9, but had little effect on its transcriptional level. Finally, weexplored the impact of curcumin for epithelial-mesenchymal transition process, and found12.5-50μmol/L of curcumin concentration-dependently up-regulated the expression ofE-cadherin and down-regulated the expression of Vimentin during epithelial-mesenchymaltransition.We also selected another papillary thyroid cancer cell line, BCPAP cell line, assupplement for the above results. We found12.5,25and50μmol/L of curcuminconcentration-dependently inhibited the growth of BCPAP cells, induced early apoptosis,down-regulated mitochondrial membrane potential. Similarly, curcumin inhibited cellattachment, spreading and migration, increased the protein level of E-cadherin and reducedthe protein level of Vimentin in BCPAP. In addition, we studied the combined action oftransforming growth factor-β (TGF-β) and curcumin on metastasis of BCPAP cells. We found0-10ng/mL of TGF-β1concentration-dependently upregulated the activity of MMP-9, andcurcumin could inhibit this effect mediated by TGF-β1. We also found that TGF-β1couldinduce Smad2/3phosphorylation in BCPAP cells, thereby activated Smads protein-dependentTGF-β signaling pathway. But curcumin could inhibit the phosphorylation of Smad2/3so asto hinder the TGF-β signal transduction fundamentally.In conclusion, this study confirmed that curcumin could inhibit the growth andmetastasis of thyroid cancer cells, and its mechanism included inhibition of MMP-9 transcription, secretion and activity, up-regulation of E-cadherin protein level, down-regulation of Vimentin protein level, thereby interfereing epithelial-mesenchymal transition,inhibiting Smad2/3phosphorylation, thus fundamentally hinder the TGF-β signal transduction.The results of this study demonstrate that curcumin might be applied to the new anti-cancerdrugs and health food for cancer prevention. |
PDF Full Text Request