Effect Of Caveolin-1Gene Silencing On Radiosensitizing And Repair Of DNA Damage In Human Zhang’s Liver Cells

Liver cancer is a serious hazard to human health cancer, the cancer incidence and mortality rank the top three, so the liver cancer radiation therapy has already also been widespread concerned by public. In the way of clinical, radiation in local control of liver cancer patients is one main important therapy way. However in the course of radiation therapy, radiation not only destructed part of liver cells but also effected radiation sensitizing of the normal liver cells, meantime, which lead to damage of the normal liver cells. So, people pay much attention to how decrease the normal cell radiation sensitivity.In recent years, research shows Caveolin-1as an important structural protein of caveolae was involved in intracellular and extracellular material exchange, a variety of special classes and lipid modulation of lipid signaling molecules and participate in enrichment and assembly of several signal transduction pathways. Studies have shown that Cav-1may play a critical role in sensing genotoxic stress and in orchestrating the response of cells to DNA damage through regulating the important molecules involved in maintaining genomic integrity.On the basis of these findings, we used Cav-1gene silencing cell line CHL-CAV7and its parental cell line CHL, to investigate the cell survival ability, cell cycle variation, DNA damage repair factor and related signal transduction factor expression after exposure X-ray radiation. We have tried to elucidate the relationship between Cav-1expression and the radiation sensitivity of liver cancer cells and clarify the possible molecular mechanism of how Cav-1influence radioactive DNA damage repair. This study aims to reveal the role of Cav-1as a platform for marker proteins of the cell membrane signal transduction in response to cellular radiation injury, and provide experimental basis for clinical treatment.The results as follows:(1) Cav-1gene silencing increased cell radiosensitivity. After exposure to0-10Gy X radiation, CHL and CHL-CAV7cells survival rate were reduced. When exposured to8Gy X radiation CHL-CAV7cells survival rate declined significantly compared with CHL cells;5Gy X irradiation induced G1phase arrest in CHL and CHL-CAV7cells, and CHL-CAV7cells G1phase arrest level higher than CHL cells.(2) Cav-1gene silencing reduce DNA damage repair. When exposured to5Gy X radiation, yH2AX、p-ATM and DNA-PKcs were expressed in both CHL and CHL-CAV7cells. However, the expression of γH2AX was higher, while p-ATM and DNA-PKcs were lower in CHL-CAV7cells than that of CHL cells.(3) Ionizing radiation promoted the interaction between Cav-1and Mdm2, which is more obvious in the CHL cells. The expression of p53was decreased after radiation in CHL-CAV7cells.Conclusion:Cav-1gene silencing increased the radiosensitivity in human Zhang’s liver cells and redused the ability of DNA damage repair by p53-Mdm2negative regulation.