Effect of 17-allylamino-17-demethoxygeldanamycin on radiosensitivity of human lung cancer cell line

Abstract

Objective To study the radiosensitizing effect of 17-allylamino-17- demethoxygeldana -mycin(17-AAG)on human non-small cell lung cancer cell line(A549 cells), and to investigate its possible mechanism. Methods The growth inhibition effect of 17-AAG on A549 cells was determined using the MTT assay. The radiosensitizing effect of the drug on cells was analyzed using the multi-target single-hit model fitting the colony survival curve. The impacts of the drug on cell aging and DNA damage repair were evaluated using β-galactosidase staining and 7-H2AX immunofluorescence, respectively. Between-group comparison was performed by paired t test or analysis of variance. Results The suppression of cell proliferation by 17-AAG was both dose-dependent and time-dependent(P = 0. 01-0. 05). The radiation group treated with the drug had a lower colony forming efficiency than the radiation-only group. When 50 nmol/L 17-AAG was applied, the radiosensitivity enhancement ratios were 1. 79(the ratio of D0 values)and 2. 30(the ratio of Dq values), respectively. The percentage of senescent cells at 72 hours after exposure was significantly higher in cells exposed to the drug and radiation of 4 Gy X-ray than in the drug-only group(30.48% vs. 9. 18%, P= 0.00)or in the radiation-only group(30.48% vs. 12.30%, P= 0. 00). Immunofluorescent staining showed that 17 - AAG delayed the DNA damage repair. Conclusions 17-AAG has growth inhibition and radiosensitizing effects on human lung cancer A549 cells. Induction of cell aging and delay of DNA damage repair may be involved in the radiosensitizing mechanism. Key words: 17-allylam ino-17-demethoxygeldanamycin; Radiosensitizing; Cell senescence; Deoxyribonucleic acid damage