LAUSR

AIMS Amplified in liver cancer 1 gene (ALC1), a recently identified oncogene, was reported to be overexpressed in esophageal cancer cell lines and identified as a target oncogene in esophageal cancer pathogenesis. However, little literature is available to illustrate its significance in cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells. The aim of the current study was to investigate the effect of ALC1 on cisplatin cytotoxicity of ESCC cells and to study the potential mechanisms. MAIN METHODS ALC1 at mRNA and protein levels were detected by qRT-PCR and western blot, respectively. Cell viability was evaluated using CCK-8 assay. Apoptosis was assessed using caspase-3/7 activity assay and flow cytometry analysis. Glycolysis level was evaluated by measuring glucose consumption and lactate production. The protein levels of p-protein kinase B (Akt) and Akt were determined by western blot. KEY FINDINGS ALC1 was highly expressed in ESCC cells compared with human normal esophageal epithelial Het-1A cells. ALC1 knockdown suppressed the viability, induced apoptosis and enhanced cisplatin cytotoxicity in ESCC cells. In addition, ALC1 knockdown inhibited glycolysis and inactivated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in ESCC cells. Mechanistically, activation of the PI3K/Akt pathway by 740Y-P blocked the effects of ALC1 knockdown on cisplatin cytotoxicity and glycolysis in ESCC cells. In contrast, inhibition of the PI3K/Akt pathway by LY294002 or glycolysis by 2-deoxyglucose resisted the effect of ALC1 overexpression on cisplatin cytotoxicity in ESCC cells. SIGNIFICANCE ALC1 knockdown enhanced cisplatin cytotoxicity of ESCC cells by inhibition of glycolysis through inactivation of the PI3K/Akt pathway.