IkappaB/NF-kappaB mediated cisplatin resistance in HeLa cells after low-dose gamma-irradiation is associated with altered SODD expression.

摘要: Fractionated γ-irradiation (15 × 2 Gy in 3 weeks) induces a cellular resistance HeLa cells against cisplatin exposure but not irradiation. The mechanisms underlying this are associated with major changes the TNFR1-dependent transduction pathway. resistant HeLa/B exhibit increased levels of NF-κB temporally independent regulation subunits NF-κB50 and NF-κB65. Blocking IκB degradation by proteasome inhibitor PSI, which abolishes release active protein, cell death much more effectively parental than cells. translocation does seem to be affected similar manner since masking sequence SN50 enhances toxicity same degree both lines overcomes drug resistance. Changes upstream signaling suggested sensitivity presence neutralizing anti-TNFR1. In cells, reduced expression 50 kDa silencer domain, SODD, is accompanied constitutive overexpression 40–42 SODD-like protein. A possible involvement SODD discussed, may shift balance between life TNF receptor pathway activation.