Antitumor Effect Of β-Elemene On Human Differentiated Thyroid Cancer Cells

Objective: To investigate the effects of β-elemene on proliferation,apoptosis,cycle,migration,angiogenesis and energy metabolism of TPC-1,K1 and FTC133 cell lines in differentiated thyroid cancer(DTC)and provide a theoretical basis for the therapeutic effect of β-elemene in DTC.Methods: DTC cell lines(TPC-1,K1 and FTC133)were dealt with different concentrations of β-elemene in this study to observe its effects on the tumor’s biological characteristics.CCK8 was used to analysis the proliferative capacity,flow cytometry was used to detect the apoptosis and cell cycles.Transwell assay was used to investigate the tumor’s invasive ability.Western blot was used to detect the expression of cell cycle,apoptosis-related proteins and VEGF A.Changes in cellular glycolysis and mitochondrial respiration were measured by Seahorse energy metabolism analyzer.Results: 1.β-elemene inhibited the proliferation of DTCThe proliferation ability of TPC-1,K1 and FTC133 cells was limited in a timeconcentration-dependent way after the treatment of β-elemene.2.β-elemene promoted the apoptosis of DTC cellsThe apoptosis ratio of TPC-1 cell was statistically higher than the control group(P<0.05)while disposed to 40 and 60μg/ml β-elemene;The apoptosis ratio of K1 was statistically higher than the control group(P<0.05)while disposed to 20 and 40μg/ml β-elemene;The apoptosis ratio of FTC133 cell was statistically higher than the control group(P<0.05)while disposed to 40 and 60μg/ml β-elemene.3.β-elemene induced the cell cycle arrest of DTC cellsTPC-1 and FTC133 cells were in a statistically higher proportion of G1 phase(P<0.05)while disposed to 60μg/ml β-elemene;When disposed to 10,20 and 40μg/ml β-elemene,statistically more K1 cells were blocked in G2/M phase(P<0.05).4.β-elemene inhibited the invasion ability of DTC cellsAfter treated with β-elemene,statistically less TPC-1,K1 and FTC133 cells went through the matrigel(P<0.05).5.β-elemene changed the expression of cycle-related,apoptosis-related proteins and VEGF A in DTC cellsWestern blot showed that,after treatment with β-elemene,the expression of CDK2,CDK6,CyclinE and bcl-2 were decreased in TPC-1 cells,and the expression level of caspase-8 and cleaved caspase-9 were increased.In K1 cells,the expression of CDK1,CyclinB1 and bcl-2 were decreased,and there was no significant difference in the expression level of caspase-8,and the expression level of cleaved caspase-9 was increased.In FTC133,the expression of CDK2,CDK6,CyclinE and bcl-2 were decreased,and there was no significant difference in the expression level of caspase-8,and the expression level of cleaved caspase-9 was increased.Moreover,the expression level of VEGF A was decreased in TPC-1,K1 and FTC133 cell lines after treated with β-elemene(P<0.05).6.β-elemene inhibited energy metabolism in DTC cellsThe Seahorse energy metabolism analyzer showed that the ECAR and OCR values of TPC-1,K1 and FTC133 cell lines were decreased after treated with β-elemene(P<0.05).And the values of glycolysis,glycolysis maximal capacity,basal OCR,maximal respiration and ATP production were all decreased in a dose-dependent manner(P<0.05).Conclusion: β-elemene has a remarkable antitumor effect on DTC cells.The mechanism is related to the inhibition of proliferation,the promotion of apoptosis,the occurrence of cycle arrest,the inhibition of cell invasion,and the reduction of angiogenesis and energy metabolism.And β-elemene could be a promising new treatment for DTC.