| Aliphatic polyamines are natural constituents of most living organisms, they play important roles in regulation of cellular growth and differentiation. It was showed that abnormal increasing in ornithine decarboxylase (ODC) activity, the key enzyme for polyamines biosynthesis and enhancing polyamines content were closely related to carcinogenesis, progression and metastasis of tumors. These data suggest that inhibition of polyamme biosynthesis is a efficient approach to treat tumor. Our previous reports showed: Difluoromethylornithine (DFMO), a irreversible inhibitor of ODC, can induce HL60 cells growth arrest and differentiation and the induced cells had low or loss potential of colony formation in soft agar and tumorigenecity in nude mice; DFMO not only inhibited growth of xenograft in nude mice but also induced apoptosis in HL-60 cells, more over our group had cloned apoptosis related gene-DF4. To investigate the molecular mechanism of apoptosis induced in tumor cell by inhibition of polyamine biosynthesis and to search for pathway of tumor therapy through apoptosis, we first induced HL-60 cells apoptosis by DFMO and observed downregulation of bcl2, and then constructed a replication defective retroviral vector expressing bcl2 antisense RNA. After it was packaged by packaging cell PA317, HL-60 cells were transduced in vitro with fresh retroviral stock produced by the PA317. The changes in growth characteristics, tumorigenicity and the effects of DFMO on the growth and apoptosis of HL-60 cells transfected with retroviral vector expressing bcl2 antisense RNA and the molecular mechanism of these changes were studied systematically. The main points of this study were summarized as follows:1. Effect of DFMO on growth and apoptosis of HL-60 cells (1) The growth of HL-60 cells treated with 5mM DFMO was arrested .
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