HPV16 E6/E7 Negatively Affect Radiosensitivity of Lung Cancer Cells

摘要：Objective Lung cancer cells associated with radioresistance are likely to give rise to local recurrence and distant metastatic relapse,but little is known about its underlying mechanisms.In the present paper,the effects of the HPV16 E6 and HPV16 E7 oncoprotein on the radiosensitivity of lung cancer cell lines were investigated.Methods The HPV16 E6 or HPV16 E7 oncoprotein was expressed by a transient transfection with pcDNA3-HPV16 E6 or pcDNA3-HPV16 E7 expression vector.Human lung cancer H2179 cells and mouse lung cancer Lewis cells were exposed to a γ-ray radiation source,cellular survival was evaluated by using a colony formation assay.The expression of HPV16 oncoproteins E6/E7,extracellular signal-regulated kinases 1/2(ERK1/2) and AKT signaling was determined by Western blot assay.VEGF secretion was determined by ELISA.Results Both HPV16 oncoproteins E6 and E7 significantly decreased radiosensitivity of H2179 cells,associated with a promotion of the ERK1/2 and AKT phosphorylation.A decrease of reactive oxygen species(ROS) and an increase of VEGF levels were observed in the cells expressing the HPV16 oncoproteins E6 and E7.Furthermore,a similar reduction of radiosensitivity mediated by the HPV16 oncoproteins E6 and E7 was also observed in a mouse lung cancer Lewis cells.Conclusion The findings indicate that the HPV16 oncoproteins E6 and E7 negatively affects susceptibility of lung cancer cells to radiotherapy via regulation of the ERK1/2 and Akt signaling pathway and VEGF expression.