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Mol Med Rep. 2018 Jul;18(1):407-414. doi: 10.3892/mmr.2018.8950. Epub 2018 May 3.

Anticancer effects of isofraxidin against A549 human lung cancer cells via the EGFR signaling pathway.

Author information

1
Breath Internal Medicine Department, The Second Clinical Medical College, Jingzhou Central Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology and Yangtze University, Jingzhou, Hubei 434100, P.R. China.

Abstract

Lung cancer is the leading cause of mortality due to tumor malignancy worldwide. In recent years, the treatment of lung cancer with chemotherapy has demonstrated notable resistance and insensitivity. Therefore, it is of great importance to investigate anti‑lung cancer drugs with high efficiency and low toxicity. In the present study, the effects of isofraxidin on lung cancer cells and the associated mechanisms were investigated. The results revealed that, in vivo and in vitro, isofraxidin exhibited marked inhibitory effects on the A549 lung cancer cell line. The results of Cell Counting kit‑8, Transwell migration and Matrigel invasion assays, and flow cytometry to determine apoptosis, revealed that isofraxidin significantly inhibited the proliferation, migration and invasion of A549 cells, and induced the cell apoptosis. Furthermore, western blot analysis demonstrated that isofraxidin treatment led to effects on the expression of apoptosis‑associated proteins, including members of the Bcl‑2 protein family, and invasion‑associated proteins, including matrix metallopeptidase (MMP)‑2 and MMP‑9, which may occur via inhibition of the expression of phosphorylated (p)‑epidermal growth factor receptor, p‑AKT and p‑extracellular signal‑regulated kinase. This regulation of protein expression may contribute to the inhibition of proliferation, migration and invasion of A549lung cancer cells by isofraxidin. In addition, despite the inhibitory effects on the A549 lung cancer cell line, the present study revealed that isofraxidin exhibited low toxicity towards BEAS‑2B normal lung epithelial cells within a certain dose range (0‑160 µM), indicating that isofraxidin may be employed for lung cancer treatment with hypotoxicity and fewer side effects. In conclusion, isofraxidin may be a novel candidate for anti‑lung cancer chemotherapy.

PMID:
29750303
DOI:
10.3892/mmr.2018.8950
[Indexed for MEDLINE]

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