Celecoxib Induced Tumor Cell Radiosensitization by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-2 Independent Mechanism

Nuclear EGFR Suppresses Ribonuclease Activity of Polynucleotide Phosphorylase through DNAPK-mediated Phosphorylation at Serine 776

“…Moreover, resistance of cancer to radiotherapy is frequently correlated with elevated EGFR expression, activity, and nuclear translocation (14). While studies have shown that ionizing radiation (IR) triggers caveolin-1-driven internalization and nuclear transport of EGFR to activate DNA-dependent protein kinase (DNAPK) in response to DNA double-strand break (DSB) repair (15)(16)(17) and that blocking IR-induced nuclear transport of EGFR by a cyclooxygenase-2 (COX-2) inhibitor, celecoxib, induces tumor cell radiosensitization (18), the mechanism by which nEGFR drives radioresistance in cancers remains elusive.…”

Cooperative Enhancement of Radiosensitivity After Combined Treatment of 17-(Allylamino)-17-Demethoxygeldanamycin and Celecoxib in Human Lung and Colon Cancer Cell Lines

“…Celecoxib is a COX-2-specific inhibitor that is currently used in clinical settings. Celecoxib is known to exert anticancer and chemo-or radiosensitizing effects by inhibiting various signaling pathways in both COX-2-dependent and -independent manners (Park et al, 2006;Dittmann et al, 2008). In addition, celecoxib interacts synergistically with other targeted agents (Shin et al, 2005;Dittmann et al, 2008).…”

The overexpression of ERCC-1 is involved in the resistance of lung cancer cells to cetuximab combined with DDP

“…When cetuximab combined with radiation, it inhibited the nuclear translocation of the complex between DNA-PK and EGFR and then delayed the DNA repair. [62][63][64] Oxaliplatin induced both DSBs and adducts. When cetuximab was combined with oxaliplatin, cetuximab reduced the expression of ERCC-1 and other genes involved in DNA replication initiation.…”