Inhibited autophagy enhance metformin induced apoptosis in oral squamous cell carcinoma / 局解手术学杂志

ABSTRACT

Objective To study the effects of metformin on proliferation and apoptosis of oral squamous cells so as to create a new path for the treatment of oral carcinoma.Methods CAL27 cells were treated with different dosage of metformin(5,10,20 mmol/L)for 24,48, and 72 hours.The number of apoptosis was detected by flow cytometry and TUNEL.The autophagic vacuole was detected by immunofluores-cence.The expression of hallmark of apoptosis and autophagy was detected by Western blot.Results Metformin could induce apoptosis in CAL27 cells.The CL-PARP and Bcl-2 expression significantly increased.In line with the apoptosis,metformin can trigger autophagy in CAL27 cells.The expression of LC3,Beclin-1 and GFP-LC3 positive autophagosomes were increased by metformin.Metformin inhibit the expression of STAT3 and mTOR signaling pathways at the same time might be the possible reasons of the autophagy.And inhibited autophagy could en-hance metformin induced Caspase-3 activity in CAL27 cells.Conclusion Inactivation of STAT3 and mTOR pathway contributes to metform-in-induced autophagy.Inhibited autophagy could enhance metformin induced apoptosis in oral squamous cell carcinoma.