Abstract Objective To investigate the radiosensitizing effect of 17AAG-cypate micelles on human non-small cell lung cancer A549 cells and its possible mechanism. Methods (1) A single-hit multi-target model formula was used to analyze the radiosensitizing effects of 17AAG-M and 17AAG-cypate-M.(2) The effects of 17AAG-cypate-M on the viability of A549 cells under laser and X-ray irradiation were analyzed by MTT assay.(3) The effect of the drugs on the cell senescence was observed by β-galactosidase staining assay.(4) The effects of different treatment conditions on DNA damage repair were analyzed by γ-H2AX immunofluorescence staining assay.(5) The expression of p-Erk1/2 and p-Akt was measured by Western blot. The paired t test was used for analyzing the differences between groups. Results Compared with the X-ray irradiation group, the X-ray+17AAG-cypate-M group had a lower mean lethal dose and a sensitization enhancement ratio greater than 1, indicating that 17AAG-cypate-M had a radiosensitizing effect. Compared with the 17AAG-M group, the 17AAG-cypate-M group showed significantly lower cell viability (P<0.01), a significantly higher percentage of aging cells (P<0.01), and significantly further delayed DNA damage repair (P<0.01). And the 17AAG-cypate-M group had lower expression of p-Erk1/2 and p-Akt than the 17AAG-M group. Conclusions Compared with 17AAG-M, 17AAG-cypate-M has a higher radiosensitizing effect on A549 cells. The mechanism might be inducing the cell senescence, delaying DNA damage repair, and inhibiting the expression of p-Erk1/2 and p-Akt.
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2017, Vol. 26 
