Effect of metformin-induced endoplasmic reticulum stress on the apoptosis of thyroid cancer TPC-1 cells / 中华内分泌代谢杂志

ABSTRACT

Objective To explore the effect of metformin on the apoptosis of thyroid cancer TPC-1 cells and its mechanism.Methods The proliferation and apoptosis of TPC-1 cells treated with different concentrations of metformin were detected using cell count kit-8(CCK-8)assay and flow cytometry respectively.Western blot and Real-time PCR were used to detect the expression of endoplasmic reticulum chaperone immunoglobulin heavy chain binding protein(Bip)and endoplasmic reticulum stress associated apoptosis protein CCAAT/enhancer-binding protein homologous protein(CHOP)and cysteinyl aspartate specific proteinase(Caspase-12)on mRNA and protein levels.TPC-1 cells were injected into nude mice to investigate the effect of metformin on the tumorigenesis in vivo.In addition,the expressions of Bip and CHOP were detected by an immunohistochemical method.Results Metformin could decrease proliferation and promote apoptosis of TPC-1 cells.Moreover,metformin increased the expression of Bip and endoplasmic reticulum stress-associated apoptosis protein Caspase-12 and CHOP,both in protein and mRNA levels.4-phenylbutyrate,the endoplasmic reticulum stress inhibitor,could reverse the metformin-induced apoptosis of TPC-1 cells.By contrast,activating endoplasmic reticulum stress by thapsigargin enhanced the metformin-mediated apoptosis.The average tumor weight and size in metformin group was significantly lower than that in the control group.Meanwhile,the metformin group had higher expression of Bip and CHOP.Conclusion Metformin may induce the apoptosis of thyroid cancer TPC-1 cells through endoplasmic reticulum stress activation.