Role of Nitric Oxide for Modulation of Cancer Therapy Resistance

摘要: Reactive nitrogen species (RNS) act as central second messengers in a balanced cellular network. While the complexity of nitric oxide (NO) signaling is far from being understood, and many controversial data can be found literature, there evidence for NO major player modulation resistance to anticancer drugs radiotherapy. Hypoxia cancer tissues causes therapy resistance, hypoxia-inducing factor-1 (HIF-1) plays predominant role hypoxia-induced resistance. NO-donating compounds sensitize tumor cells by inhibiting HIF-1 mediated transcription hypoxic cells. Among plethora other genes, HIF-1-induced multidrug gene 1, MDR1, angiogenesis-inducing vascular endothelial growth factor (VEGF). NO-mediated down-regulation glutathione antioxidant stress response genes well inhibition DNA repair proteins also contributes sensitivity tumors chemo- Hypoxic tend accumulate with mutations suppressor gene, TP53. activates wild-type p53 protein peroxynitrite-mediated damage exerts resistance-modulating effects on wild-type, but not mutant p53. Furthermore, antiapoptotic factor, NF-κB, inhibited donors. Thereby, only enhances susceptibility radiotherapy suppresses NF-κB-mediated metastasis-regulating genes.