UmorsTable 1 Overview of HiF-1-mediated chemo-/radioresistance mechanismsResistance phenotype DNA repair pathway activation DNA repair pathway

UmorsTable 1 Overview of HiF-1-mediated chemo-/radioresistance mechanismsResistance phenotype DNA repair pathway activation DNA repair pathway activation DNA repair pathway activation DNA repair pathway activation DNA repair pathway activation DNA repair pathway activation Metabolic reprogramming Metabolic reprogramming Metabolic reprogramming Apoptosis inhibition Apoptosis inhibition Apoptosis inhibition Autophagy activation Autophagy activation Autophagy activation Autophagy activation Autophagy activation Autophagy activation Molecular basis (if recognized) XPA DNA-PK XPA Cell model Lung cancer cells Mouse embryonic fibroblasts Germ cell tumors Hepatocellular carcinoma cells Gastric cancer cells Mouse mesenchymal stromal cells Lung cancer cells Colorectal cancer cells Multiple myeloma cells Colon cancer cells Gastric cancer cells Gastric cancer cells Colon cancer cells Lung cancer cells Lung cancer cells Osteosarcoma cells Lung cancer cells Mouse mesenchymal stromal cells Therapies Cisplatin etoposide Cisplatin Radiotherapy Chemo-/radiotherapy Radiotherapy Cisplatin RiP-dependent necroptosis Bortezomib Chemo-/radiotherapy 5-Fluorouracil Chemo-/radiotherapy Radiotherapy Cisplatin Radiotherapy Radiotherapy Silver nanoparticle Radiotherapy Reference 36 40 41 42 43 44 47 51 53 58 59 60 70 71 72 30 73DNA-PK, H2AX GLUT1 GLUT1 LDHA STAT3, TCF4 P53 Survivin, Bax, caspase 3/8 MiRNA20, Bcl2 BNiP3, Beclin-1 Beclin-1, c-Jun LC3ii mTOR/Pi3KAbbreviations: DNA-PK, DNA-dependent protein kinase; RiP, receptor-interacting protein.of DNA damage induced by chemo-/radiotherapy. Also, Yang et al31 reported that the hepatocarcinoma cells exhibited Cement Inhibitors Reagents greater activity of DNA harm repair pathway than normal cells and Stover et al32 reported that activated DNA repair pathway is really a significant lead to of chemo-/radioresistance in tumor cells. Therefore, immediately after exposure to chemotherapeutic drugs and radiation, quite a few cancer cells could steer clear of death by way of the activation of DNA repair pathway. Fortini et al33 reported that chemo-/radiotherapy might induce single-stranded DNA breaks (SSBs) or doublestranded DNA breaks (DSBs), which have to be repaired or must start off apoptosis. The repair of SSBs is carried out by major pathways: base excision repair (BER), poly-ADPribose polymerase (PARP-1), and both XPA and XPD are the important molecules Dodecylphosphocholine References within the BER course of action. DSBs are much more damaging on cell survival than SSBs and are robust activators of apoptosis due to the fact cell death may be induced by the persistence of DSBs if not repaired. To preserve genomic stability and survival, cells have developed DNA damage response (DDR) to manage DSBs in accordance with Fortini et al.33 Fortini et al33 also observed that cells respond to DSBs promptly and accurately, that three steps may be important: initial, the harm have to be detected by each ataxia telangiectasia mutated (ATM) and ataxia telangiectasia RED3 connected (ATR); second, damaged proteins have to match in to the transmembrane proteins on the cells; and finally, cells react to repair DSBs under the function from the DNAdependent protein kinase (DNA-PK) and histone H2AX,when the DNA repair is failed, Li et al34 proposed that the ATM/ATR complicated activates P53, its downstream molecule, which induces apoptosis. A large number of studies showed that HIF-1 could boost the capacity of DNA damage repair by way of the regulation of DNA repair pathway, thus leading for the chemo-/ radioresistance in tumor cells. For example, Um et al35 identified that HIF-1 contributed to resista.