Abstract: Objective To investigate the effect and mechanism of metformin on the apoptosis of papillary thyroid carcinoma TPC-1 cells.Methods TPC-1 cells were treated with different doses(0mmol/L,1mmol/L,5mmol/L,10mmol/L,20mmol/L and 40mmol/L) of metformin for 24h.3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide(MTT) assay was used to measure the proliferation viability of cell lines.Annexin Ⅴ-FITC/PI flow cytometry was used to detect the rate of apoptosis of TPC-1 cells treated by different concentrations of metformin.At the same time,the adenosine 5’-monophosphate-activated protein kinase（AMPK） inhibitor Compound C was added to the 40mmol/L group,and its effect on the apoptosis of TPC-1 cells was observed.Western blotting was performed to determine the protein expressions of p-AMPK and Caspase-9.Results Compared with the 0mmol/L group,the proliferation viability of TPC-1 cells in 1mmol/L and 5mmol/L groups had no significant changes(P>0.05).But 10mmol/L,20mmol/L and 40mmol/L metformin all significantly inhibited the proliferation activity of TPC-1 cells in a dosedependent manner(P<0.05).Compared with the 0 mmol/L group,the different concentrations of metformin could significantly increase the apoptosis rate of TPC-1 cells(P<0.001).However,after the addition of Compound C,the apoptosis rate of TPC-1 cells in 40mmol/L group was significantly lower than that before(P<0.001).Compared with the 0mmol/L group,the different concentrations of metformin could increase the protein expression of p-AMPK and Caspase-9.Conclusion Metformin can induce apoptosis of TPC-1 cells.The process of apoptosis induced by metformin is probably related to the activation of AMPK signaling pathway,which may be mediated by Caspase-9.

Key words: Metformin, Papillary thyroid carcinoma, Apoptosis, Aadenosine 5’-monophosphate-activated protein kinase, Caspase-9