Cross-resistance of anti-AIDS drugs and inhibition of apoptosis

  Objective   HIV-1 associated neoplasias is modulated by viral and host factors.As the anti-HIV-1 agents call trigger mechanisms involved in chemoresistance, to test whether prolonged in vitro treatment of Jurkat cells with nelfinavir alters sensitivity of lymphoma cells to antitumor agents used for AIDS-associated maliglancies.

  Methods   To select the humanacute T-cell leukemia cell line(Jurkat)resistant to nelfinavir(Jurkat^rN)by exposure to increasing concentrations of nelfinavir(up to 14 μm)for 50 days.The cytotoxicity assays of the compounds for the cells were based on the cell viability.The number of the viable cells is determined by a tetrazolium-dye method.

  Results   The cells are found to be about 5-fold resistant to d4T and K-37 and about 2.5-fold resistant to CDDP, VCR, DOX and VP-16, when compared with parental Jurkat cells.The expression of the antiapo ptotic gene Bcl-2 is increased in Jurka^rN when determined by flow cytometry.

  Conclusion   These results demonstrate that prolonged in vitro treatment of Jurkat lymphoma cells with nelfinavir results in the development of resistance to other anti-AIDS drugs and antitumor agents in association with inhibition of apoptosis and increases expression of Bcl-2.