To our knowledge, we are the first to experimentally demonstrate that (1) metformin and dextromethorphan can downregulate the expression and inhibit the activity of CHRNA7, respectively, and (2) combination of these reagents can counteract nicotine-enhanced ESCC tumor-initiating capacity, and therefore inhibit ESCC progression. The gene discussed is CHRNA7; the disease is esophageal squamous cell carcinoma.