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ObjectiveAt present, there are relatively few studies on the inhibitory effect of ursolic acid (UA) on the proliferation of thyroid cancer cells. This paper intends to explore the inhibitory effect and mechanism of ursolic acid on the proliferation of TPC-1 cells in thyroid papillary carcinoma.MethodsAfter adhering TPC-1 cells to the wall, the original medium was discarded and added ursolic acid medium without fetal bovine serum (0, 2, 4, 8, 16, 32 μmol/L, respectively, with 0 μmol/L as the control), and then the culture medium without cells was used as blank. The proliferation inhibition rate of TPC-1 cells was detected by CCK8 reagent at different times (24 h, 48 h); Flow cytometry was used to detect the apoptosis rate; JC1 kit was used to detect the changes of mitochondrial membrane potential (MMP) of TPC-1 cells after ursolic acid was applied; Fluorescent probe DCFH-DA was used to detect reactive oxygen species in TPC-1 cells after ursolic acid intervention; Flow cytometry was used to detect the protein expression of survivin and vascular endothelial growth factor (VEGF) in cells. RT-PCR assay detected the expression of survivin and VEGF mRNA in TPC-1 cells after the intervention of ursolic acid at different concentrations.ResultsThe inhibitory rate of 2, 4, 8, 16 and 32 mol/L ursolic acid on TPC-1 cells was significantly higher than that of 0 mol/L (P<0.01), and the inhibitory rate of 48 h ursolic acid on TPC-1 cells was significantly higher than that of 24 h (P<0.05). Therefore, the TPC-1 cell inhibition rate was positively correlated with ursolic acid concentration and the time (P<0.05). The apoptosis rates of 0 mol/L, 4 mol/L and 8 mol/L ursolic acid were (4.13±0.61)%, (6.53±0.65)% and (13.13±1.59)%, respectively. With the increase of the concentration, the apoptosis rate of TPC-1 cells increased gradually (P<0.05). The relative expression levels of survivin, VEGF protein and mRNA of 4 and 8 mol/L ursolic acid were significantly lower than those of 0 mol/L (P<0.05), and the expression levels of 8 mol/L ursolic acid was significantly lower than that of 4 mol/L (P<0.05).ConclusionUrsolic acid can effectively inhibit the proliferation and induce the apoptosis of TPC-1 cells, and its inhibitory induction pathway is related to the expression of survivin and VEGF in cells.
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BACKGROUND: Although so many experimental trials have been done to improve the redifferentiation and responsiveness of radioiodide therapy, they have not yet yielded any satisfactory results. As statins inhibit both farnesylation and geranylgeranylation, they have been reported to have an antineoplastic and redifferentiation effect in experimental and clinical studies. In this study, we investigated the relationship between statins and the alteration of the NIS expression and, TPC-1 cell apotosis to evaluate the possibility of using statins as adjuvant therapeutic agents for papillary thyroid cancer. METHODS: We used the TPC-1 cell lines for our experiments. Cell viabilities were measured by CCK-8. The degrees of apoptosis and, the expressions of NIS mRNA and NIS protein were measured by flow cytometry, semi quantitative RT-PCR and Western blot assay. RESULTS: Increased levels of NIS mRNA and NIS protein were observed under therapeutic blood concentrations (concentrations of simvastatin: 20, 50, 80 nM, concentrations of atorvastatin: 50, 80,110 nM), but the dose-response relationship was only manifested within simvastatin. The TPC-1 cells showed a concentration dependent decrease of viability and an increase of apoptosis not under therapeutic blood concentrations, but under excessively high concentrations (after treatment with 10-50 microM of atorvastatin and with 1-10 microM of simvastatin). CONCLUSION: The results of this study show that effective therapeutic blood concentrations of simvastatin and atorvastatin can give a favorable effect on the NIS expression under effective therapeutic blood concentrations. Therefore, we demonstrated the possibility that simvastatin and atorvastatin might have an important role as adjuvant therapeutic agents to improve the responsiveness of radioiodide therapy for papillary thyroid cancer. Further studies are needed to clarify this issue.