Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy
Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy
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DOI：
10.2147/ijn.s193676
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Li, Qiang
中科院分区：
文献类型：
--
作者：
Li, Feifei;Li, Zihou;Li, Qiang
背景：钆基纳米颗粒（GdNPs）已被用作临床放疗研究中的治疗增敏剂；然而，GdNPs放射致敏效应的生物机制尚未确定。本研究采用超小氧化钆纳米晶体（GONs）研究其在x射线照射下对非小细胞肺癌（NSCLC）细胞的放射增敏作用及其生物学机制。方法与材料：采用多元醇法合成GONs。x射线照射后的羟基自由基生成、氧化应激和克隆存活被用来评估GONs的放射增敏作用。通过体外研究DNA双链断裂、细胞周期、细胞凋亡和自噬发生率，探讨x射线照射下GONs的放射致敏生物机制。结果：x射线照射后，GONs诱导非小细胞肺癌细胞产生羟基自由基和氧化应激，并呈剂量和浓度依赖性。对于接受研究的NSCLC细胞，GONs的增敏剂增强率在19.3%至26.3%之间，与单独照射处理的细胞相比，其存活率为10%。在细胞培养基中添加3-甲基腺嘌呤可降低细胞自噬发生率，提高细胞存活率，支持x射线照射下GONs促进NSCLC细胞自噬的观点。结论：本研究探讨了GONs对NSCLC细胞放射增敏作用的生物学机制，并首次提供了x射线照射后GONs通过激活细胞抑制自噬途径产生放射增敏作用的证据。
Background: Gadolinium-based nanoparticles (GdNPs) have been used as theranostic sensitizers in clinical radiotherapy studies; however, the biomechanisms underlying the radiosensitizing effects of GdNPs have yet to be determined. In this study, ultra-small gadolinium oxide nanocrystals (GONs) were employed to investigate their radiosensitizing effects and biological mechanisms in non-small-cell lung cancer (NSCLC) cells under X-ray irradiation.Method and materials: GONs were synthesized using polyol method. Hydroxyl radical production, oxidative stress, and clonogenic survival after X-ray irradiation were used to evaluate the radiosensitizing effects of GONs. DNA double-strand breakage, cell cycle phase, and apoptosis and autophagy incidences were investigated in vitro to determine the radiosensitizing biomechanism of GONs under X-ray irradiation.Results: GONs induced hydroxyl radical production and oxidative stress in a dose-and concentration-dependent manner in NSCLC cells after X-ray irradiation. The sensitizer enhancement ratios of GONs ranged between 19.3% and 26.3% for the NSCLC cells under investigation with a 10% survival rate compared with that of the cells treated with irradiation alone. Addition of 3-methyladenine to the cell medium decreased the incidence rate of autophagy and increased cell survival, supporting the idea that the GONs promoted cytostatic autophagy in NSCLC cells under X-ray irradiation.Conclusion: This study examined the biological mechanisms underlying the radiosensitizing effects of GONs on NSCLC cells and presented the first evidence for the radiosensitizing effects of GONs via activation of cytostatic autophagy pathway following X-ray irradiation.