Scutellarin improves the radiosensitivity of non‐small cell lung cancer cells to iodine‐125 seeds via downregulating the AKT/mTOR pathway

• Published in: Thoracic cancer Vol. 12; no. 17; pp. 2352 - 2359
• Main Authors: He, Guang‐hui, Xing, Dian‐jin, Jin, Die, Lu, Yue, Guo, Lei, Li, Yu‐liang, Li, Dong
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01.09.2021; John Wiley & Sons, Inc; Wiley
• Subjects: A549 Cells; Animals; Apigenin - pharmacology; Apoptosis; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - radiotherapy; Cell cycle; Cell growth; Cell Proliferation - drug effects; Chemotherapy; Down-Regulation; Flow cytometry; Glucuronates - pharmacology; Humans; Iodine; iodine radioactive seed; Iodine Radioisotopes - pharmacology; Liver cancer; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - radiotherapy; Male; Medical prognosis; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; mTOR protein; non‐small cell lung cancer; Original; Proto-Oncogene Proteins c-akt - metabolism; Scutellarin; TOR Serine-Threonine Kinases - metabolism; Transplants & implants; Tumors; China; Scutellarin; mTOR protein; non-small cell lung cancer; iodine radioactive seed
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.14077

Background In our previous study, we indicated that scutellarin (SCU) induced an anticancer effect in A549 cells. However, whether SCU regulates the radiosensitivity of non‐small cell lung cancer (NSCLC) and its related mechanism is still unclear. Methods In this study, we explored the anticancer effect induced by iodine‐125 (125I) and SCU at a sensitizing concentration in A549 and H1975 cells. Cellular apoptosis and proliferation were detected by flow cytometry, Bcl‐2/Bax expression level, cell cycle, CCK‐8, and EdU staining. A tumor model using nude mice was also carried out to investigate the combined effect of 125I and SCU in vivo. In addition, the expression level of AKT/mTOR pathway was detected to investigate whether it is linked to the anticancer effect of 125I and SCU. Results SCU at a sensitizing concentration promoted the 125I‐induced apoptosis and antiproliferative effect in A549 and H1975 cells. Moreover, the same results were obtained in vivo. Based on our findings, the AKT/mTOR pathway was significantly downregulated after combined treatment with 125I and SCU. Conclusions The results of our study suggested that SCU promotes the anticancer effects induced by 125I in NSCLC cells by downregulating the AKT/mTOR pathway and lays a foundation for future application of this combined treatment. Scutellarin (SCU) enhanced inhibition of 125I‐induced proliferation, promoted 125I‐induced apoptosis, and boosted 125I‐induced tumor inhibition in vivo in non‐small cell lung cancer (NSCLC) cells, as well as enhanced downregulation of the 125I‐induced AKT/mTOR pathway.