Objective: To explore the effect of the expression change of acetyl-CoA synthetase 2 (ACSS2) on the sensitivity of esophageal squamous cell carcinoma (ESCC) to cisplatin (DDP) and relevant mechanism. Methods: ACSS2 expression was detected in tumor and paracancerous tissues collected from 40 cases of ESCC by immunohistochemistry and western blotting. In vitro verification of ACSS2 expression difference was performed by Western blotting in ESCC cell line and normal esophageal squamous Het-1A cell line. ACSS2 downregulated and overexpressed cell strains were constructed by liposome transfection of siRNA-ACSS2 or lentivirus transfection of LV-ACSS2 into TE-1 cells. CCK8 assay was used to detect the change of IC50 value of DDP by downregulating the expression of ACSS2. Meanwhile, the effect of ACSS2 interference on TE-1 cell apoptosis was tested by flow cytometry before and after DDP treatment (5 μg/mL). In addition, Western blotting was carried out to detect the expression of proteins related to PI3K/AKT signaling pathway and apoptosis-related protein cleaved-Caspase-3. Results: Immunohistochemistry and Western blotting results showed that the expression intensity of ACSS2 in ESCC tissue was significantly higher than that in paracancerous normal tissue (P<0.001). In vitro test indicated that the expression of ACSS2 in ESCC cell line was obviously higher than that of normal esophageal squamous Het-1A cell line. CCK8 results showed that IC50 of TE-1 cells was remarkedly downregulated after siRNA-ACSS2 treatment (all P<0.05). Flow cytometry results showed that the apoptosis rate of ESCC cells was obviously decreased by inhibiting ACSS2 expression (P<0.01), which, however, increased significantly under the combined treatment of 5 μg/mL DDP and ACSS2 interference (all P<0.001). Furthermore, according to the results of Western blotting, expression levels of ACSS2, p-PI3K and p-AKT were upregulated in TE-1 cells after DDP treatment. Simultaneously, under DDP treatment, targeted inhibition of ACSS2 expression resulted in significant decrease of p-PI3K and p-AKT expression, but obvious increase of apoptosisrelated protein of cleaved-Caspase-3; while overexpression of ACSS2 could maintain the activation of PI3K/AKT signaling pathway and reverse the expression of cleaved-Caspase-3 effectively. Conclusion: ACSS2 is involved in regulating the sensitivity of ESCC to DDP by regulating activation of PI3K/AKT signaling pathway and expression of cleaved-Caspase-3.

［Key words］acetyl-CoA synthetase 2； cisplatin； esophageal squamous cell carcinoma； chemosensitivity； PI3K/AKT