Effects Of Glucose Concentration On The Inhibition Of Proliferation,apoptosis And Cell Cycle Arrest Induced By Metformin In Breast Cancer

Aims: As a common malignant tumor of Chinese women,breast cancer is also the main cause of death of female patients.The incidence of breast cancer is increasing year by year,which seriously threatens the physical and mental health of Chinese women.It has been confirmed that type 2 diabetes is a risk factor for breast cancer,and breast cancer patients with diabetes have higher histological grade and poorer efficacy of neoadjuvant chemotherapy than those with normal blood glucose.As a first-line drug for the treatment of type II diabetes,metformin can not only effectively control the blood glucose level of patients,but also has been found to inhibit breast cancer and improve the prognosis,suggesting that the anti-cancer effect of metformin may be related to the blood glucose level.Therefore,this paper will explore the effect and mechanism of metformin on breast cancer cells in different glucose concentrations.Methods:(1)The effects of metformin on the proliferation,apoptosis and cell cycle of MCF-7,MDA-MB-231 and MDA-MB-468 cells at different glucose concentrations: trypan blue assay was used to observe the effects of metformin on the proliferation of breast cancer cells at different glucose concentrations,and flow cytometry was used to detect the effects of metformin on cell apoptosis and cell cycle.(2)The effects of metformin on intracellular ROS of MCF-7,MDA-MB-231 and MDA-MB-468 cells at different glucose concentrations: flow cytometry was used to detect the effects of metformin on intracellular ROS.(3)The effects of metformin on the expression of ROS scavenger protein TRX and related proteins in MCF-7,MDA-MB-231 and MDA-MB-468 cells at different glucose concentrations: Western Blot was used to assess the expression of TRX,TRXR,TXNIP and other proteins in breast cancer cells.Results:(1)Metformin can inhibit the proliferation of breast cancer cells in a time-dependent manner,and the inhibitory effect is more obvious in low glucose condition.(2)Compared with high glucose condition,metformin can significantly induce apoptosis and cell cycle arrest in low glucose condition.(3)Compared with high glucose condition,metformin can significantly induce intracellular ROS accumulation in low glucose condition.(4)In low glucose condition,metformin can significantly inhibit the expression of TRX protein.Conclusion: Our conclusion confirmed that metformin can inhibit the proliferation of breast cancer cells,and low glucose concentration can increase the sensitivity of breast cancer cells to metformin,and such anti-cancer effects might be functioning by promoting ROS accumulation,inducing apoptosis and cell cycle arrest.