【摘要】 目的　体外研究奈非那韦耐性细胞株对其它抗艾滋病药及抗癌药的反应及与细胞凋亡的关系。方法　通过将成人T细胞白血病细胞株Jurkat培养于含有奈非那韦浓度不断增加直至 14 μm的培养液中培养 50d以获得耐奈非那韦的亚系细胞株JurkatrN。药敏试验用四唑嗡染色法 (类似XTT法 )并用流式细胞仪检测抗凋亡蛋白Bcl -2在母本和耐性Jurkat细胞中的表达。结果　发现JurkatrN细胞对d4T及新近报道的抗艾滋病药K -3 7的交叉耐性与母本细胞相比提高到 5倍左右。对抗肿瘤药CDDP ,VCR ,DOX和VP -16的交叉耐性也提高到 2 5倍以上。并且耐性细胞中心Bcl -2蛋白的荧光密度增加。结论　在用HIV -1蛋白酶抑制物奈非那韦作用后 ,Jurkat细胞对其它抗艾滋病药及抗肿瘤药产生了交叉耐性并且抗凋亡蛋白Bcl-2的表达增加更多还原

【Abstract】 ObjectiveHIV-1 associated neoplasias is modulated by vir al and host factors.As the anti-HIV-1 agents call trigger mechanisms involved in chemoresistance,to test whether prolonged in vitro treatment of Jurkat cell s with nelfinavir alters sensitivity of lymphoma cells to antitumor agents used fo r AIDS-associated maliglancies. MethodsTo select the human acute T- cell leukemia cell line (Jurkat) resistant to nelfinavir (Jurkat\+rN) by exposur e to increasing concentrations of nelfinavir (up to 14?μm) for 50 days.The cyt otoxicity 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. ResultsThe 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 com pared with parental Jurkat cells.The expression of the antiapoptotic gene Bcl-2 is increased in Jurka\+rN when determined by flow cytometry. ConclusionThese results demonstrate that prolonged in vitro treatment of Jurkat lymphoma cells with nelfinavir results in the develo pment of resistance to other anti-AIDS drugs and antitumor agents in association with inhibition of apoptosis and increases expression of Bcl-2.更多还原