Effects Of Recombinant Human Tumor Necrosis Factor-alpha On HL-60 Cell And Its Xenografts In Nude Mice

Tumor necrosis factor-alpha, a pleiotropic protein, was the first cytokine to be employed for cancer biotherapy. It was known to exhibit a number of pharmaceutical actions such as anti-inflammatory , anti-tumor, immunological regulation and so on. As a promising anti-tumor agent, it had attracted more and more attention. Previous studies of anti-tumor effect of TNF- α more emphasized on melanocarcinoma, hepatoma, lung cancer, nasopharyngeal carcinoma, laryngeal carcinoma and so on, however it was not reported yet that the anti-tumor effect of TNF-α on leukemia. We had demonstrated that expression of TNF- α was significantly up-regulated in As₂O₃-inducing apoptotic HL-60 cells. At the same time we had demonstrated that antisense phosphorothioate oligodeoxynucleotide (APSODN) could rescue As₂O₃ -inducing apoptosis of HL-60 cells. So we hypothesized mat endogenous TNF- α played an important role in the apoptosis of HL-60 induced by As₂O₃ .On the basis of that previous study, we chose HL-60 cells as objective and tried to reveal the effect of rhTNF-α on it There had been some reports about the effect of rhTNF-α on HL-60 cells in vitro, but no reports in vivo. In the present experiment, we studied the effects of rhTNF-α on HL-60 cell in vitro and its anti-tumor effects on xenografts of HL-60 cells in nude mice.The subjects of the thesis were focused on the following aspects:The first part of this experiment was in vitro cell experiment MTT and colony forming assay were used to examine the effects of rhTNF- α on the proliferation of HL-60 cells; AO/EB (acridine orange - ethidium bromide) staining, Annexin -V flow cytometry analysis and TUNEL assay were used to examine apoptotic cells.The second part was to treat the xenografts of HL-60 cells in nude mice with...