[Killing effect of interleukin-18-enhanced FasL-expressing colon cancer cells on human hepatocytes in vitro].

Objective To investigate the influence of mutual interactions between FasL expressed by colon carcinoma cells and endogenous cytokines interleukin-18 on liver metastasis and invasion of human colon cancer cells. Methods Using immunohistochemical streptavidin-biotin complex （SABC） method, the expressions of Fas receptor and Fas ligand in SW620 colon carcinoma cells and Chang liver cells were observed so as to provide morphological evidence for the functions of Fas receptor and Fas ligand. In an effort to examine the cytotoxicity of effector cells, CytoTox 96（R） Non-Radioactive Cytotoxicity Assay was adopted to measure the LDH releasing value after the SW620 cells were co-cultured with Chang liver cells. Results It was shown that the Fas ligand of colon carcinoma SW620 cells was positive and the positive substances were distributed in the cell membrane and cytoplasm, and the Fas receptor of colon earcinma SW620 cells was negative. The Fas receptor of Chang liver cells turned out to be positive and the positive stbstances were distributed in the cell membrane, and the Fas ligand of Chang liver cells was negative. At 6 hours after co-culture of IFN-γ-stimulated Chang liver cells with interleukin-18-stimulated （for 36 h） SW620 cells or unstimulated SW620 cells, the cytotoxicity of SW620 cells to IFN-stimulated Chang liver cells at effector-totarget ratios of 10：1, 5：1 , 2.5： 1 and 1.25 ： 1 was 68.3 %, 49. 8 %, 21. 1 %, 9. 7 % （F =76. 87, P 〈 0.05）and 32.7%, 21. 8% ,11. 1% ,6. 7%（F =7. 27, P 〈 0. 05） ,respectively. The non-radioactivecytotoxicity assay showed that the apoptotic rate of Chang liver cells was remarkably increased with the increase of planting concentration of SW620 after the SW620 cells were co-cultured with Chang liver cells. The cytotoxicity was significantly enhanced by interleukin-18. Conclusion The FasL expression.of human colon cancer cells may be regulated by endogenous interleukin-18 in the host microenvironment and enhance the liver colonization competence of eolon cancer cells through induction of apoptosis in the Fas-expressing hepatocytes. Key words: Iinterleukin-18;  Colonio neoplasms;  SW620 cells;  Chang cells;  Antigens, CD95;  Fas ligand protein