Radiosensitivity Enhancement Of Human Lung Adenocarcinoma Cell Line A549by Glu-GNPs

Objective:Radiotherapy holds an important place in the comprehensive treatment of malignancies, and it is involved in more than2/3tumor patients. Radiosensitivity is the key to radiotherapy of tumor. The use of radiosensitizer can reduce radiotherapy dose effectively and enhance radiosensitivity of tumor cells. Therefore it can increase effectiveness of radiotherapy and lower injury to normal tissues and organs. Gold nanoparticles have been proved to enhance radiosensitivity of many tumor cells so to improve the efficacy, but the report of lung cancer by gold nanoparticles was seldom, and the mechanism was not clear. To study radiosensitivity enhancement and the mechanism of human lung adenocarcinoma cell line A549by thio-glucose bound gold nanoparticles (Glu-GNPs), and offer new platform for the treatment of lung cancer.Methods:1. MTT assay was used to determine the effect of gold nanoparticles in low concentration(≤20nmol/L) with or without8Gy X-rays on the survival of A549cells.2. The effect of radiotherapy enhancement on A549cells by Glu-GNPs was measured by clonal survival.3. The distribution of cell cycle and the change of apoptosis rate were assayed by flow cytometric method(FCM).Results:1. With different concentrations(5、10、15、20nmol/L)of Glu-GNPs on A549cells for48hours, the cell viability was99.1±0.85%、98.1±1.22%、97.5±1.31% and96.8±1.003% respectively. There was no obvious difference between these data (P>0.05). With different concentrations(0、5、10、15、20nmol/L)of Glu-GNPs on A549cells for24hours, and associated with radiation for24hours, the cell inhibition ratio was18.38±0.39%、26.29±0.54%、38.76±0.62%、46.34±0.85% and47.38±0.35% respectively. In the0-15nmol/L range, the inhibition enhanced with the increase of concentration.2. There was radiosensitivity enhancement of13nm Glu-GNPs on A549cells and the sensitization enhancement ratios were1.93and1.10according to Dq and Do respectively.3. With Glu-GNPs, the cell cycle changed, decreased in S phase from24.11±6.1% to13.68±0.22%(P<0.05), and increased in G2/M phase from6.53±2.05% to13.01±1.15%(P<0.05). Radiation and Glu-GNPs could induce apoptosis respectively, the rates of apoptosis were13.46±1.99%and7.64±1.43%, and the effect was enhanced to21.43±1.04%when they were combined.Conclusion:There was no distinct restrain on the survival of A549cells by Glu-GNPs in low concentrations for48hours. But with X rays, the cell inhibition enhanced with the increase of concentration in the0-15nmol/L range. With Glu-GNPs, A549cells turned from S phase resist to radiotherapy to radiosensitive G2/M phase. Glu-GNPs and radiation could induce apoptosis respectively, the induction effect enhanced when they were combined. Through clonal survival, there was radiotherapy enhancement for Glu-GNPs on lung adenocarcinoma cell line A549, and the mechanism may are restrain of repair of sublethal damage, blocking cells at G2/M and inducing apoptosis.