Abstract: Objective:To explore the effect of paclitaxel (PTX) and cisplatin (DDP) on the expression of NKG2D ligands of hu-man esophagus carcinoma cell EC 9706and on the cytotoxicity of cytokine-induced killer (CIK) cells, as well as to discuss its molecu-lar mechanisms. Methods:The half maximal inhibitory concentration (IC50) values of PTX and DDP against EC 9706cells for 24h were measured by MTT assay. The expression levels of NKG 2D ligands (MICA, MICB, ULBP1, ULBP2, and ULBP 3) on the EC 9706 cell surface before and after 24h culture with 1/2 IC50 of PTX or DDP were assayed by flow cytometry. Cytotoxicity of CIK cells against EC9706cells before and after 24h culture with 1/2 IC50 PTX or DDP was analyzed by lactate dehydrogenase release assay at an effector to target cell ratio (E:T) of20:1 and 30:1, respectively. The expression levels of DNA damage repair genes (ATM, ATR, CHK1, CHK2, and p 53) of EC9706cells before and after 24h incubation with1/2 IC50 PTX or DDP were detected by quantitative fluorescent PCR.Results:The IC 50 values of PTX and DDP were 10and 5 μ g/mL, respectively. MICB, ULBP 2, and ULBP 3 on EC 9706cells were upregulated after 24h culture with 1/2 IC50 PTX (P<0.05), and the expression levels of MICA, MICB, ULBP2, and ULBP 3 were higher after 24h culture with 1/2 IC50 DDP (P<0.05). Cytotoxicity of CIK cells against EC 9706cells cultured with 1/2 IC50 of PTX or DDP at E:T of 20:1 and 30:1 was significantly enhanced compared with those untreated (P<0.05). The expression levels of DNA damage repair genes did not significantly increase after 24h treatment with 1/2 IC50 PTX (P>0.05), whereas ATM, ATR, CHK 1, and CHK 2 were over -expressed after24h treatment with 1/2 IC50 DDP (P<0.05). Conclusion:PTX or DDP can enhance the susceptibility of EC9706cells to CIK cell-mediated lysis by upregulating the expression of NKG2D ligands through activating DNA damage repair genes.