Abstract
Melanoma is known to be radioresistant and traditional treatments have been intractable, and therefore, novel approaches are required to improve therapeutic efficacy. Gold nanoparticles (GNPs) have been explored as radiosensitizers, while most of the research in the area has focused on the enhancement occurred in the kilovoltage (kV) range. The present study investigated the possible application and biological mechanism of gold nanorods (GNRs) for sensitization at clinically relevant MV X-ray energies. A375 melanoma cells were treated by gold nanorods (GNRs) with or without irradiation. The anti-proliferative impacts of the treatments were measured by MTT assay. The cellular uptake and intracellular localization were analyzed by transmission electron microscopy. Radiosensitizing effects were determined by a colony formation assay. Apoptosis and cell cycle data were measured by flow cytometry. DNA damage was estimated by γ-H2AX expression measured with immunofluorescent staining.
Results showed that the addition of GNRs enhanced the radiosensitivity of A375 cells with a dose-modifying factor (DMFSF2) of 1.14, increasing more radiation-induced DNA double-strand breaks and apoptosis. DNA flow cytometric analysis indicated that GNRs plus irradiation significantly induced G2/M phase arrest in A375 cells.
In Conclusions: GNRs could sensitize melanoma A375 cells to 6 MV X-ray irradiation, and this was mainly through increasing the DNA double-strand breaks, in addition to the induction of a higher proportion of cells within the G2/M phase. The interaction of GNRs and high energy commonly used in the clinic may provides another rational for the potential application of GNRs in the treatment of cancer..
