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In the present study, the inhibitory effect of transmembrane Tim-3 on hepatocellular carcinoma Hepa1-6 cells and the potential application of Tim-3 on immune system of Institute of Cancer Research (ICR) mice loaded with Hepa1-6 hepatocellular carcinoma was investigated. The animal model was established via inoculation of Hepa1-6 hepatocarcinoma cells at the hind thigh of ICR mice. Recombinant vector plasmids were transfected at the same site for gene therapy by injection to observe the inhibitory effect of Tim-3 on tumor growth. A panel of genes from tumor tissues at various time intervals was analyzed by reverse transcription-polymerase chain reaction. Flow cytometry was used to evaluate the proliferation and cytotoxicity of splenocytes after Tim-3 transfection. Synergistic effects of Tim-3 with tumor abnormal protein-1 (TAP1) was also studied. It was revealed that the growth of tumor was significantly suppressed after the transfection of Tim-3. In the presence of Tim-3, the proliferation of splenocytes and cytolysis in the early phase of tumor development was significantly enhanced, and this antitumor effect was further improved by the synergistic effect of Tim-3 with TAP1. Therefore, the membrane-type Tim-3 may behave as an effective immunoregulator to enhance antitumor immune responses. Furthermore the present findings suggest that antitumor immunity was improved by the combined effect of Tim-3 and TAP1.

Antitumor effect of membrane-type Tim-3 on hepatocellular carcinoma Hepa1-6 cells of ICR mice