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β-elemene inhibits non-small cell lung cancer cell migration and invasion by inactivating the FAK-Src pathway
Hongbo Zhang1, Shaobing Li2, Jun Bao3
1Department of Radiology, The First Affiliated Hospital of USTC, Division of Life and Medicine, University of Science and Technology of China, Hefei, Anhui 230031, P.R. China.
Abstract:
Despite sustained effort, the prognosis of lung cancer remains poor and the therapeutic responses are limited. Cell movement ability is a prerequisite for lung cancer metastasis, which involves focal adhesion kinase (FAK)-mediated cell migration and invasion via complex formation with Src. Hence, FAK-Src signaling might be an effective target for anti-cancer treatment. β-elemene, the major component of elemene extracted from Curcuma Rhizoma, exhibits broad-spectrum anti-tumor properties. However, the role of β-elemene in lung cancer cell motility and its possible mechanism remain unknown. Herein, the role of β-elemene in the migration and invasion of two non-small cell lung cancer (NSCLC) cell lines was investigated by performing wound-healing and Transwell assays. The mRNA expression levels of genes associated with motility, including RhoA, Rac1, Cac42, matrix metalloprotease (MMP)2 and MMP9, were examined by reverse transcription-quantitative polymerase chain reaction. To determine whether β-elemene acts through FAK-Src signaling, western blotting was performed and the levels of phosphorylated FAK and Src were detected. The results indicated that β-elemene inhibited the migration and invasion of A549 and NCI-H1299 (H1299) cells, while the motility-associated genes were de-regulated following exposure to β-elemene. Furthermore, β-elemene decreased the activity of FAK and Src. Overall, these results suggest that β-elemene potentially inhibits NSCLC through FAK-Src signaling.
Insights
Beta-elemene effectively inhibits non-small cell lung cancer (NSCLC) cell migration and invasion. This compound targets focal adhesion kinase (FAK)-Src signaling pathways, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Lung cancer prognosis remains poor with limited therapeutic options.
- Cell migration and invasion are critical for lung cancer metastasis.
- Focal adhesion kinase (FAK)-Src signaling is implicated in cancer cell motility.
Purpose of the Study:
- To investigate the role of beta-elemene in non-small cell lung cancer (NSCLC) cell motility.
- To elucidate the underlying mechanism of beta-elemene's anti-cancer effects, specifically its impact on FAK-Src signaling.
Main Methods:
- Wound-healing and Transwell assays were used to assess cell migration and invasion.
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyzed motility-associated gene expression.
- Western blotting detected phosphorylated focal adhesion kinase (FAK) and Src levels.
Main Results:
- Beta-elemene significantly inhibited the migration and invasion of A549 and NCI-H1299 (H1299) NSCLC cell lines.
- Exposure to beta-elemene altered the expression of motility-related genes, including RhoA, Rac1, Cac42, MMP2, and MMP9.
- Beta-elemene treatment reduced the activity of FAK and Src signaling pathways.
Conclusions:
- Beta-elemene demonstrates potent anti-motility effects in NSCLC cells.
- The mechanism involves the inhibition of FAK-Src signaling.
- Beta-elemene represents a promising therapeutic agent for NSCLC treatment.
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