Objective    To determine the effect of cadmium on the proliferation of anaplastic thyroid carcinoma FRO cells

and investigate the underlying mechanisms. Methods      Western blotting was used to detect the expression of G protein-coupled estrogen receptor 1 (GPER1) in FRO cells

MCF-7 cells and MAD-231 cells respectively. After the above cells were separately treated with different concentrations of CdCl2 (0

0.25

0.50

0.75 and 1.00 nmol/L) for 48 h

the cell viability was evaluated by MTT assay. The FRO cells were treated by 0.5 mmol/L CdCl2 for 0

5

10

15 or 30 min

the levels of phosphorylated ERK1/2 and Akt were analyzed by Western blot analysis. FRO cells were treated with G15 or transfected with the designed and synthesized RNA interference against GPER (GPER-RNAi)

the levels of phosphorylated ERK1/2 and Akt were analyzed by Western blotting respectively. FRO cells were treated with GPER1 inhibitor G15

ERK1/2 inhibitor PD98059 (PD) and PI3K-Akt inhibitor LY294002 (LY)

alone or in combination

and MTT assay was used to determine the cell proliferation. Results     The expression level of GPER1 was significantly lower in the MAD-MB-231 cells than in the MCF-7 and FRO cells. Low-dosed CdCl2 treatment for 48 h promoted the proliferation of the FRO cells and MCF-7 cells

but had no effect on that of the MAD-MB-231 cells. However

CdCl2 at high concentrations suppressed the cell proliferation in the 3 kinds of cells. After the cells were treated by 0.5 mmol/L CdCl2 for different periods

the levels of phosphorylated ERK1/2 and Akt reached peak at 15 min in FRO cells

and the levels of phosphorylated ERK1/2 and Akt were decreased significantly in FRO cells (P0.05) when the cells were treated with GPER1 inhibitor G15

transfected with GPER-siRNA

ERK1/2 inhibitor PD or Akt inhibitor LY. Conclusion      Cadmium promotes the proliferation of anaplastic thyroid carcinoma FRO cells through GPER1-ERK/AKT pathway.