The antitumor immunity of FasL-transfected Lewis lung carcinoma enhanced by cyclooxygenase-2 inhibitor

• Main Authors: Ren-Shiang Jhou, 周仁祥
• Other Authors: Shye-Jye Tang
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/33719154880866707166

碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 92 === Abstrsct The Fas ligand (FasL) induces programmed cell death via interaction with its receptor Fas. It has been proposed that expression of FasL can confer immune privilege to some organs, allowing them to kill infiltrating lymphocytes and inflammatory cells. However, a number of studies have shown that when tumors express FasL that can recruit neutrophils to induce inflammation. The Lewis lung carcinoma express FasL (FasL-LLC) which can elicit antitumor activity. But the antitumor activity is not good enough that we expected. In this study, C57/BL6J mice were challenged sc with FasL-LLC that mixed with LLC, and tumor growth is reduced. The survival rate of these mice is 40%. We demonstrate FasL-LLC can recruit neutrophils to induce bystander effect. And we find that LLC expressed Cyclooxygenase-2 (COX-2), VEGF, EGFR and TGF-β by RT-PCR. Tumor overexpreses COX-2 that can promote tumor metastasis and angiogenesis, and can inhibit tumor apoptosis and immune response. Thus, we used cox-2 inhibitor, indomethacin (IND) to inhibit FasL-LLC and LLC COX-2 activity, in this study. We find that the COX-2 activity of LLC and FasL-LLC can be inhibited 86 % and 84% by IND, respectively. In animal study, mice which drink water with IND challenged pretreated-IND LLC, and we observed the meaning of tumor growth is reduced. In other animal study, Mice challenged pretreated-IND FasL-LLC, then re-challenged pretreated-IND LLC, the tumor growth is reduced comparing to control. In CTL assay, we observed IND can promote CTL activity of effector cell , when target cell co-culture with effector cell. We suppose that IND can enhance the antitumor activity induced by FasL-LLC, and the CTL activity can be enhanced when the COX-2 activity of LLC is inhibited by IND. Therefore, the COX-2 inhibitor can be apply to combine with gene therapy to form a complex therapy.