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Radiosensitizing Effect of P2X7 Receptor Antagonist on Melanoma in Vitro and in Vivo.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2017 Jun 01; Vol. 40 (6), pp. 878-887. Date of Electronic Publication: 2017 Mar 24. - Publication Year :
- 2017
-
Abstract
- Melanoma is highly malignant, and generally exhibits radioresistance, responding poorly to radiation therapy. We previously reported that activation of P2X7, P2Y6, and P2Y12 receptors is involved in the DNA damage response after γ-irradiation of human lung adenocarcinoma A549 cells. However, it is not clear whether these receptors are also involved in the case of melanoma cells, although P2X7 receptor is highly expressed in various cancers, including melanoma. Here, we show that P2X7 receptor antagonist enhances radiation-induced cytotoxicity in B16 melanoma cells in vitro and in vivo. We confirmed that these cells express P2X7 receptor mRNA and exhibit P2X7 receptor-mediated activities, such as ATP-induced pore formation and cytotoxicity. We further examined the radiosensitizing effect of P2X7 receptor antagonist Brilliant Blue G (BBG) in vitro by colony formation assay of B16 cells. γ-Irradiation dose-dependently reduced cell survival, and pretreatment with BBG enhanced the radiation-induced cytotoxicity. BBG pretreatment also decreased the number of DNA repair foci in nuclei, supporting involvement of P2X7 receptor in the DNA damage response. Finally, we investigated the radiosensitizing effect of BBG on B16 melanoma cells inoculated into the hind footpad of C57BL/6 mice. Neither 1 Gy γ-irradiation alone nor BBG alone suppressed the increase of tumor volume, but the combination of irradiation and BBG significantly suppressed tumor growth. Our results suggest that P2X7 receptor antagonist BBG has a radiosensitizing effect in melanoma in vitro and in vivo. BBG, which is used as a food coloring agent, appears to be a promising candidate as a radiosensitizer.
- Subjects :
- Animals
Cell Line, Tumor
DNA Damage
DNA Repair
Humans
Male
Melanoma, Experimental metabolism
Melanoma, Experimental pathology
Mice, Inbred C57BL
Purinergic P2X Receptor Antagonists pharmacology
Radiation-Sensitizing Agents pharmacology
Receptors, Purinergic P2X7 genetics
Rosaniline Dyes pharmacology
Tumor Burden drug effects
Gamma Rays therapeutic use
Melanoma, Experimental therapy
Purinergic P2X Receptor Antagonists therapeutic use
Radiation-Sensitizing Agents therapeutic use
Receptors, Purinergic P2X7 metabolism
Rosaniline Dyes therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1347-5215
- Volume :
- 40
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 28344198
- Full Text :
- https://doi.org/10.1248/bpb.b17-00083