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Both the anti-and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain.ABT263 (Navitoclax),a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL,Bcl-2 and Bcl-w has entered clinical trials for cancer treatment.But the anticancer mechanisms of ABT-263 have not been fully elucidated.In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms.Treatment with ABT-263 dose-dependently suppressed the viability of 3 human esophageal cancer cells with IC50 values of 10.7±1.4,7.1±1.5 and 8.2±1.6 μmol/L,in EC109,HKESC-2 and CaES-17 cells,respectively.ABT-263 (5-20 μmol/L) dose-dependently induced G1/G0-phase arrest in the 3 cancer cell lines and induced apoptosis evidenced by increased the Annexin Ⅴ-positive cell population and elevated levels of cleaved caspase 3,cleaved caspase 9 and PARP.We further demonstrated that ABT-263 treatment markedly increased the expression of p21waf1/Cip1 and decreased the expression of cyclin D1 and phospho-Rb (retinoblastoma tumor suppressor protein) (Ser780) proteins that contributed to the G1/G0-phase arrest.Knockdown of p21waf1/Cip1 attenuated ABT-263-induced G1/G0-phase arrest.Moreover,ABT-263 treatment enhanced pro-survival autophagy,shown as the increased LC3-Ⅱ levels and decreased p62 levels,which counteracted its anticancer activity.Our results suggest that ABT-263 exerts cytostatic and cytotoxic effects on human esophageal cancer cells in vitro and enhances pro-survival autophagy,which counteracts its anticancer activity.