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Updated: Jan 27, 2026

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Long-Term Exposure to Oroxylin A Inhibits Metastasis by Suppressing CCL2 in Oral Squamous Cell Carcinoma Cells
Wei-Ting Ku1, Jiun-Jia Tung2,3, Tony Jer-Fu Lee4,5
1Master Program of Pharmacology and Toxicology, Department of Medicine, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan. 106721104@gms.tcu.edu.tw.
Abstract:
Oroxylin A (Oro-A), the main bioactive flavonoid extracted from Scutellaria radix, has been reported to inhibit migration in various human cancer cell models. In this study, we further explored the anti-migration effects of Oro-A on oral squamous cell carcinoma (OSCC) cells and investigated the underlying mechanisms. A 24-h (short-term) exposure of OSCC cells to non-cytotoxic concentrations (5⁻20 μM) of Oro-A significantly suppressed cell migration according to a wound-healing assay. Furthermore, a 30-day exposure (long-term) to Oro-A (20 μM), which did not exhibit a cytotoxic effect on OSCC cells, significantly suppressed cell migration more than short-term Oro-A exposure. To uncover the molecular mechanisms underlying the inhibitory effect of long-term Oro-A exposure on OSCC migration, a cDNA microarray and the Ingenuity software were used. Overall, 112 upregulated and 356 downregulated genes were identified in long-term Oro-A-exposed cells compared with untreated OSCC cells. Among them, 75 genes were reported to be associated with cancer cell migration. Consistent with the cDNA microarray results, we found that the expression levels of several cell migration-related genes, such as LCN2, ID-1, MDK, S100A9 and CCL2, were significantly decreased in long-term Oro-A-exposed OSCC cells using a quantitative real-time polymerase chain reaction (Q-PCR) assay. The Western blotting and enzyme-linked immunosorbent assay (ELISA) results also demonstrated that CCL2 expression at the mRNA and protein levels was significantly decreased in long-term Oro-A-exposed OSCC cells compared with untreated OSCC cells. Moreover, the expression levels of downstream CCL2 targets, including p-ERK1/2, NFκB, MMP2, and MMP9, were also decreased in long-term Oro-A-exposed OSCC cells. Further, Oro-A treatment suppressed in vivo metastasis. These results suggest that long-term Oro-A treatment inhibits metastasis via CCL2 signaling in OSCC cells.
Insights
Oroxylin A (Oro-A) significantly inhibits oral squamous cell carcinoma (OSCC) migration and metastasis. Long-term Oro-A treatment suppresses cancer cell migration by downregulating CCL2 signaling pathways.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Oroxylin A (Oro-A), a flavonoid from Scutellaria radix, shows anti-migration effects in cancer.
- Oral squamous cell carcinoma (OSCC) is a significant global health concern with migratory potential.
Purpose of the Study:
- To investigate the anti-migration effects of Oro-A on OSCC cells.
- To elucidate the molecular mechanisms behind Oro-A's anti-migratory action in OSCC.
Main Methods:
- Wound-healing assays for cell migration assessment.
- cDNA microarray and Ingenuity software for gene expression analysis.
- Quantitative real-time PCR (Q-PCR), Western blotting, and ELISA for validating gene and protein expression (CCL2, p-ERK1/2, NFκB, MMP2, MMP9).
Main Results:
- Short-term and long-term Oro-A exposure significantly inhibited OSCC cell migration.
- Long-term Oro-A treatment led to significant downregulation of migration-related genes, including CCL2.
- Oro-A suppressed CCL2 signaling pathway components and downstream targets, inhibiting in vivo metastasis.
Conclusions:
- Long-term Oroxylin A treatment effectively inhibits OSCC cell migration and metastasis.
- The anti-metastatic effect of Oro-A is mediated through the downregulation of the CCL2 signaling pathway.
- Oro-A demonstrates potential as a therapeutic agent for OSCC treatment.
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