Effects of specific cytotoxicity T lymphocyte activated by interleukin-27 gene modified DC and loaded with esophageal tumor lysate on growth of transplantation tumor of human esophagealcarcinoma in nude mice

Objective　To investigate the effect of specific cytotoxicity T lymphocyte (CTL) activated by IL-27 gene modified DC and loaded with esophageal tumor lysate on the growth of transplantation tumor of human esophageal carcinoma in nude mice, and study the effect of IL-27 on cancer cell apoptosis and its mechanisms. Methods　With gene transfection method, human DCIL-27 cells secreting IL-27 were successfully obtained. After the nude mouse model of human esophageal carcinoma transplantation tumor was reproduced, the mice were immunized with specific CTL activated by IL-27 gene modified DC loading with esophageal tumor lysate (DCIL-27+Ag). Thirty nude mice were divided into PBS group, Tnaive group, DC+Tnaive group, DCIL-27+Tnaive group and DCIL-27+Ag+Tnaive group (6 each). The volume, weight and inhibition rate of transplantation tumors were measured. The cell cycle and apoptosis rate of transplantation tumors at G0/G1, S and G2/M stages were determined by flow cytometry. The expression of Fas and caspase-3 protein were also detected by flow cytometry. Results　RT-PCR showed that the subunits of IL-27, namely p28 and EBI3, were expressed in DCIL-27 cells, and it proved that gene transfection was successful. The volume and weight of transplantation tumors in nude mice of DCIL-27+Ag+Tnaive group were significantly smaller than those in other treatment groups and control group. The inhibition rate was 58.28%, which was much higher than that in other therapy groups and control group (P<0.01). Flow cytometry showed that the proliferation index of transplantation tumor tissue with specific CTL activated by DCIL-27+Ag was 23.92%±1.60% ,which was evidently lower than that in other therapy groups and control group (P<0.01). The apoptosis rate of cells in the transplantation tumors with specific CTL activated by DCIL-27+Ag was 32.78%±0.83%, which was significantly higher than that in other therapy groups and control group (P<0.01). Flow cytometry showed also that the expressions of Fas and caspase-3 protein in the transplantation tumor tissue with specific CTL activated by DCIL-27+Ag were significantly higher than those in other groups (P<0.01). Conclusions　Specific CTL activated by IL-27 gene modified DC loading with esophageal tumor lysate possesses great cytotoxic effects on esophageal carcinoma of tumor-bearing mice in vivo and it is able to inhibit the proliferation and enhance the apoptosis of esophageal carcinoma cells through Fas/FasL pathway in vivo. DOI: 10.11855/j.issn.0577-7402.2014.08.03