| Summary: | 碩士 === 國立成功大學 === 生物化學研究所 === 97 === Hepatocellular carcinoma (HCC, also called hepatoma) is one of the most prevalent malignancies in the world, and the prognosis of hepatoma is poor. There is accumulating evidence showing that tumor specific tolerance influences tumor progression. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme of tryptophan metabolism, is important in tumor progression and can contribute to tumor immune escape. Over-expression of IDO can be observed in the tumor-draining lymph node. This findings imply that blockage of IDO may have the therapeutic efficacy on the progression of hepatoma. Our previous results have demonstrated that IDO shRNA has therapeutic effect on inhibiting the growth of tumors implanted subcutaneously in several animal tumor models. However, the immunological environment is quite different when tumor is implanted subcutaneously. We established an orthotropic hepatoma animal model by directly inoculating ML14a cells into the liver. The tumor was formed at day 7 after intra-hepatic injection. We found that expression of IDO was elicited compared with the sham group in the mesenteric lymph node. We then treated the mice with IDO shRNA via gene gun and sacrificed them at the defined time intervals to measure the size of liver tumor. Treatment of IDO shRNA exerted therapeutic efficacy in the orthotropic hepatoma model. To further investigate the possible mechanism, we performed Immunohistochemical staining and found that there were more tumor-infiltrating lymphocytes and higher cytotoxic lysis percentage in the IDO shRNA group, suggesting that treatment of IDOshRNA may trigger an immunological response. Furthermore, we observed that IDO shRNA vaccination also has therapeutic efficacy in a metastatic tumor model. In the future, combination of the IDO inhibitor, Dextro-1-Methyl Tryptophan (D-1MT), with IDOshRNA may be further explored to enhance the therapeutic effect in the orthotropic hepatoma model.
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