Objective To observe the effects of different concentrations of metformin on proliferation,apoptosis,invasion,and PTEN expression of human breast cancer cells,and to explore its mechanism. Methods The human breast cancer cell line SK-BR-3 was divided into four groups: 0 mmol/L group,5 mmol/L group,10 mmol/L group,and 20 mmol/L group with treatment of corresponding concentrations of metformin. CCK-8 was used to detect the inhibition rate of cell proliferation,Annexin V-FITC/PI double staining method was used to detect the apoptotic rate of each group,Transwell invasion test was used to detect the invasive ability of each group,q RT-PCR was used to detect the PTEN gene of each group,and Western blotting was used to detect the PTEN protein of each group. Results The inhibition rates of cell proliferation in the 0 mmol/L group,5 mmol/L group,10 mmol/L group,and 20 mmol/L group were 0.0% ± 0.0%,23.7% ± 2.2%,43.2% ± 2.9%,and 63.9% ± 5.6%,and the apoptotic rates were 5.1% ± 0.2%,18.2% ± 1.9%,26.3% ± 2.0%,and 40.1% ± 2.6%,respectively. The number of cell penetrating the membrane in the 0 mmol/L group,5 mmol/L group,10 mmol/L group and 20 mmol/L group were 170 ± 23,112 ± 14,74 ± 9,and 30 ± 5,respectively. The relative expression levels of PTEN mRNA in the 0 mmol/L group,5 mmol/L group,10 mmol/L group,and 20 mmol/L group were 1.01 ± 0.04,2.89 ± 0.27,4.12 ± 0.23,and 5.45 ± 0.49,and the relative expression levels of PTEN protein were 0.13 ± 0.05,0.41 ± 0.06,0.61 ± 0.10,and 0.94 ± 0.11,respectively. Significant differences were found in the above indexes between groups(all P < 0.05). Conclusion Metformin of 5,10,and 20 mmol/L can regulate the proliferation,apoptosis and invasion of human breast cancer cells. Metformin may regulate the proliferation,apoptosis and invasion of breast cancer cells by up-regulating the expression of PTEN. [ABSTRACT FROM AUTHOR]