Compelling data arising from tumour samples or in vitro studies have emerged to link aberrantly activated receptor tyrosin kinases (RTKs) with chemoresistance to 5-Fu,11, 12 and inhibitors of NF-κB and Akt have demonstrated synergism with 5-Fu in ESCC.11, 13 Meanwhile, melatonin has been reported to inhibit MAPKs, Akt and NF-κB pathways.7, 14 These evidences prompted us to hypothesize that melatonin may enhance sensitivity to 5-Fu in ESCC cells. The gene discussed is AKT1; the disease is esophageal squamous cell carcinoma.