Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, P.R. China.
Breast Disease Diagnosis and Treatment Center, Qingdao Center Medical Group, Qingdao, Shandong, P.R. China.
IUBMB Life. 2020 May;72(5):1012-1022. doi: 10.1002/iub.2242. Epub 2020 Feb 6.
Quercetin, a widely distributed bioflavonoid, plays a role in combating diverse human cancers including non-small cell lung cancer (NSCLC). However, the role of quercetin in reversing the radioresistance of NSCLC cells and its underlying mechanism are far from being elucidated.
Radiation-resistant NSCLC cell lines were established. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-16-5p and WEE1 G2 checkpoint kinase (WEE1) mRNA in radiation-resistant cells. After being treated with different concentrations of quercetin and different doses of X-ray, cell proliferation and apoptosis were monitored by CCK-8 assay, colony formation assay, and flow cytometry, respectively. Ultimately, the targeting relationship between miR-16-5p and WEE1 was verified via a dual fluorescent reporter gene assay.
The expression of miR-16-5p was down-regulated in radiation-resistant cells, while the expression of WEE1 was up-regulated. Quercetin enhanced the radiosensitivity of NSCLC cells in a dose- and time-dependent manner. Furthermore, quercetin treatment increased the expression of miR-16-5p and decreased the expression of WEE1. The function of quercetin was reversed by miR-16-5p inhibitors or the transfection of WEE1 overexpressing plasmids.
In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR-16-5p and WEE1.
槲皮素是一种广泛分布的生物类黄酮，在对抗包括非小细胞肺癌（NSCLC）在内的多种人类癌症中发挥作用。然而，槲皮素在逆转 NSCLC 细胞放射抵抗中的作用及其潜在机制仍远未阐明。
建立耐辐射的 NSCLC 细胞系。通过定量实时 PCR（qRT-PCR）检测耐辐射细胞中 miR-16-5p 和 WEE1 G2 检查点激酶（WEE1）mRNA 的表达。用不同浓度的槲皮素和不同剂量的 X 射线处理细胞后，分别通过 CCK-8 测定法、集落形成测定法和流式细胞术监测细胞增殖和凋亡。最终，通过双荧光报告基因检测验证 miR-16-5p 与 WEE1 之间的靶向关系。
耐辐射细胞中 miR-16-5p 的表达下调，而 WEE1 的表达上调。槲皮素以剂量和时间依赖的方式增强 NSCLC 细胞的放射敏感性。此外，槲皮素处理增加了 miR-16-5p 的表达，降低了 WEE1 的表达。miR-16-5p 抑制剂或 WEE1 过表达质粒的转染逆转了槲皮素的作用。
总之，槲皮素通过调节 miR-16-5p 和 WEE1 的表达增强了 NSCLC 细胞的放射敏感性。
