Biomarkers for enhancing the radiosensitivity of nasopharyngeal carcinoma (NPC)
| Biomarkers | Potential mechanism of radiosensitization of NPC | Methods | References |
|---|---|---|---|
| NFBD-1 | Induction of a complete loss of nuclear foci formation, DNA repair defects, and genomic instability | Use of Lentivirus-mediated shRNA targeting NFBD 1 to silence the expression of NFBD 1 gene in CNE-1 cells | 11–13 |
| COX-2 | Reduction of G2/M phase arrest in order not to be fully repaired after receiving radiation | Use of shRNAmir lentiviral vector to silence the expression of COX-2 gene | 22–24 |
| GP96 or GDF-15 | Elevation of the proportion of the cells in radiosensitive G2-M phase | Use of siRNA to knockdown the gp96 and GDF-15 in NPC-radioresistant cells | 26,27 |
| GnT-V | Arrest of cell cycle G2-M and reduction of Bcl-2/Bax ratio | Use of Lipofectamine 2000 to transfect the plasmid of antisense GnT-V cDNA into CNE-2 cells | 30,31 |
| Jab1/CSN5 | Arrest of cell cycle G2-M | Use of T83 (a new 4-arylidene curcumin analogue) to inhibit the expression of Jab1 in NPC cells | 39–41 |
| DNA topoisomerase I | Relationship with the circadian rhythm of tumor hypoxia and G2/M phase arrest | Administration of Topotecan (DNA topoisomerase I-targeted drug) into xenografted human NPC model through peritoneal injection | 45,46 |
| Nitric oxide synthases (NOS) | Direct cellular toxicity or interaction with NO reactive species that increase apoptosis | Use of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay to detect the expression of inducible nitric oxide synthase | 50 |
| EGFR and IGF-1R | Decrease of the expression of NPC cyclins and blocking cell cycles | Use of plasmid or virus transfection to combine short hairpin RNA segments to insulin-like growth factor 1 receptor and to epidermal growth factor receptor | 54,55 |
| VEGF | Reduction of tumor angiogenesis that inhibit cancer cell growth, prevent metastasis, and decrease resistance to therapy | Use of valsartan (an AT1R antagonist that can inhibit VEGF expression and secretion in NPC cells) | 61,62 |
| LMP-1 | Interference of signal pathways, which are abnormally activated by LMP1, including NF-κB, AP-1, and STAT3 signal pathways | Use of phosphorothioate-modified “10–23” DNAzyme, namely, DZ1, to downregulate the expression of LMP1 in NPC cells | 70,71 |
| Protein kinase CK2 | It exerts its anti-apoptotic effects through the phosphorylation of a series of factors, but the mechanism of radiosensitization is unknown right now | Use of RNAi technique to downregulate the protein kinase CK2α expression in NPC cells | 73 |
| Bcl-2 | Inhibition of many apoptotic signals induced apoptosis, promotion of cell survival, and disorder of regulatory mechanism of apoptosis in vivo | Use of RNAi technology to reduce the expression of Bcl-2 protein | 76–78 |
| Notch signaling pathway | Decrease of the proportion of cancer stem cells and inhibition of tumor growth | Use of γ-secretase inhibitors to inhibit Notch signaling | 80,85,86 |