Characterization of the enhanced apoptotic response to azidothymidine by pharmacological inhibition of NF-kB.

摘要: The Aims: present study addresses the issue of enhanced apoptotic response to AZT following co-treatmentwith an NF-kB inhibitor. Main methods: To investigate this issue, different cell lines were assayed for susceptibility AZT-mediated apoptosiswithout orwith addition theNF-kB inhibitor Bay-11-7085. For further investigation,U937 cellswere selected as good-responder cells combination treatment with 32 or 128 μM AZT, and 1 Bay-11-7085. Inhibition activation by Bay-11-7085 in treated was through Western blot analysis p65 expression EMSA. Involvement themitochondrial pathway apoptosis mechanisms underlying improved effect co-treatment, evaluated assaying the cytochrome c release mitochondrial membrane potential (MMP) status using JC-1 dye. Moreover, the transcriptional activity both anti- pro-apoptotic genes U937 after treatment was quantitatively real-time PCR. Key findings: We found that combined induced high levels cytochrome MMP collapse association evident changes the Bcl-2 family. Overexpression Bcl-2 significantly suppressed sensitization an enhanced apoptotic co-treatment inhibitor. Significance: new findings suggest a regimen based on plus could represent chemotherapeutic tool retrovirus-related pathologies.present inhibitor.