The Radiosensitizing Effects Of MEK/ERK Inhibitor U0126in NSCLC Cells And Its Mechanism

PurposeMEK/ERK signaling pathway has been widely studied, which correlates withradiation effects. We investigated the effects of MEK/ERK inhibitor, U0126treatmenton the response of human non-small cell lung cancer (NSCLC) cell lines, H1299andH460cells to irradiation (IR), and found the ways to achieve the enhancedradiosensitizing activity of U0126in spite of the different genetic background ofNSCLC cells.Methods and MaterialsTwo kinds of human NSCLC cell lines, H1299and H460with different geneticbackground were used. The effects of U0126on survival fraction, DNA repair andIR-induced senescence with single and fractionation procedures were analyzed.ResultsIn single procedure, with the inhibition of MEK/ERK signaling pathway, cellproliferation decreased and cells were blocked in G1-phase. Lower survival fraction,more increased γ-H2AX foci and senescence were observed only in irradiated H1299cellswith U0126treatment. However, more obvious decrease in proliferation and enhancementof senescence were observed in both cell lines with fractional irradiation followingtreatment of U0126. The radiosensitizing effects can be got by the cell cycle redistributionand treatment of U0126combined with fractional irradiation in both NSCLC cell linesdespite the different genetic background.ConclusionsCell cycle redistribution and treatment of U0126combined with fractionation procedures were efficient ways to enhance the radiosensitizing effects of U0126in spite ofthe different genetic background of NSCLC cells. Our results demonstrated the possibilityof MEK/ERK inhibitor, U0126as an effective radiosensitizer in the future tumorradiotherapy.