Effect of cisplatin and paclitaxel on the cytotoxicity of cytokine-in-duced killer cells on esophagus carcinoma and its molecular mecha-nisms
10.3969/j.issn.1000-8179.20150396
- VernacularTitle:顺铂和紫杉醇对CIK细胞杀伤食管癌细胞活性的影响及其分子机制研究
- Author:
Jiazhuan MEI
;
Hong XU
;
Guiju LIU
;
Jizhi ZHAO
- Publication Type:Journal Article
- Keywords:
esophagus carcinoma;
paclitaxel;
cisplatin;
cytokine-induced killer cells;
NKG2D ligands;
DNA damage repair genes
- From:
Chinese Journal of Clinical Oncology
2015;(12):608-613
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of paclitaxel (PTX) and cisplatin (DDP) on the expression of NKG2D ligands of hu-man esophagus carcinoma cell EC9706 and 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 EC9706 cells for 24 h were measured by MTT assay. The expression levels of NKG2D ligands (MICA, MICB, ULBP1, ULBP2, and ULBP3) on the EC9706 cell surface before and after 24 h culture with 1/2 IC50 of PTX or DDP were assayed by flow cytometry. Cytotoxicity of CIK cells against EC9706 cells before and after 24 h culture with 1/2 IC50 PTX or DDP was analyzed by lactate dehydrogenase release assay at an effector to target cell ratio (E:T) of 20:1 and 30:1, respectively. The expression levels of DNA damage repair genes (ATM, ATR, CHK1, CHK2, and p53) of EC9706 cells before and after 24 h incubation with 1/2 IC50 PTX or DDP were detected by quantitative fluorescent PCR. Results:The IC50 values of PTX and DDP were 10 and 5μg/mL, respectively. MICB, ULBP2, and ULBP3 on EC9706 cells were upregulated after 24 h culture with 1/2 IC50 PTX (P<0.05), and the expression levels of MICA, MICB, ULBP2, and ULBP3 were higher after 24 h culture with 1/2 IC50 DDP (P<0.05). Cytotoxicity of CIK cells against EC9706 cells 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 24 h treatment with 1/2 IC50 PTX (P>0.05), whereas ATM, ATR, CHK1, and CHK2 were over-expressed after 24 h treatment with 1/2 IC50 DDP (P<0.05). Conclusion:PTX or DDP can enhance the susceptibility of EC9706 cells to CIK cell-mediated lysis by upregulating the expression of NKG2D ligands through activating DNA damage repair genes.
