BCL2 and esophageal cancer: Additionally, metformin blocks cell cycle in G0/G1 phase in esophageal cancer cell lines by reducing the expression of cyclin D1, Cdk4 and Cdk6 [33], and causes autophagy and apoptosis by downregulating Stat3 (signal transducer and activator of transcription 3), resulting in a reduced expression of Bcl-2 [34].