Quercetin radiosensitizes non‐small cell lung cancer cells through the regulation of miR‐16‐5p/WEE1 axis

Abstract

Background 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. Method 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. Results 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. Conclusion In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR‐16‐5p and WEE1.

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…Quercetin dose-dependently suppressed HGF- and TGFα-induced migration of hepatocellular carcinoma cells by inhibiting the signaling pathway of AKT, but not p38 MAPK [ 413 ]. In non-small cell lung carcinoma models, quercetin inhibited proliferation and anchorage-independent growth by inhibiting the Src-mediated Fn14/NF-ĸB pathway both in vitro and in vivo [ 408 ] and improved the radiosensitivity of these cells by altering the expression of miR-16-5p and Wee1 [ 414 ]. In vivo, lung adenocarcinoma appearance was delayed and increased non-neoplastic body weight gain in mice with tumor oxidative stress after daily treatment with quercetin was observed [ 420 ].…”

Detection of antitumoral effects of quercetin through protein synthesis associated with argyrophilic nucleolar-regulating region

“…Like many other molecules that share a flavone ring, quercetin affects immunity by acting mainly on leukocytes and targeting many intracellular signal kinases and phosphatase, enzymes, and membrane proteins that are often very important for a cellular-specific function. 32 Herbal medicines lead cancer cells to apoptosis by blocking the nuclear factor kappa B (NF-kB) pathway, increasing CD95L signaling, and increasing CD95L expression, tyrosine kinase, angiogenesis, and cell inhibition. 33 Many pharmacological properties of quercetin have been extensively investigated and have been reported to block the progression of various human tumors, such as oral cancer and breast cancer.…”

Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients

“…The expression of miR-452-5p was signi cantly increased in 387 clinical lung squamous cell carcinoma specimens [37] and renal cell carcinoma tissues [38], whereas it was downregulated in 1007 prostate cancer samples [39]. MiR- 16-5p has been proposed to function as a tumour suppressor and it was downregulated in non-small cell lung cancer cell lines [40], breast cancer samples [41], hepatocellular carcinoma tissues [42], chordoma tissues [43] and glioma tissues [44]. It was also downregulated in the plasma of gastric cancer patients [45].…”