In Vitro Inhibition of Migration and Adhesion in Cholangiocarcinoma Cells by Ovalitenin A through PI3K Modulation
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Abstract
Ovalitenin A, a chalcone extracted from the roots of Millettia brandisiana Kurz, has exhibited cytotoxic properties in various human cancer cells. However, the effects of this on cholangiocarcinoma (CCA), an aggressive malignancy of the bile duct epithelium, are still not well understood. This study investigated the anti-metastatic potential of ovalitenin A and its associated molecular mechanisms in CCA cells. Sulforhodamine B (SRB), wound-healing, and adhesion assays were used to test cell viability, migration, and adhesion, respectively. Western blotting was performed to quantify phosphorylated PI3K and VEGF proteins, and qRT-PCR was used to measure MMP-9 and TIMP-1 mRNA. Ovalitenin A suppressed the proliferation of CCA cells in a concentration-dependent manner. Following 24 hours of treatment, it markedly diminished cell migration and adhesion. Network pharmacology analysis found 32 common targets between ovalitenin A and CCA utilizing the SwissTargetPrediction and GeneCards databases. Moreover, protein–protein interaction analysis revealed a robust association among these targets, indicating the involvement of PI3K-related signaling pathways. PIK3CA and MMP-family proteins were prioritized as candidate targets based on their centrality within the network and their well-established roles in CCA progression, metastasis, and extracellular matrix remodeling. As predicted, treatment of ovalitenin A reduced the levels of phosphorylated PI3K and VEGF proteins and lowered the ratio of MMP-9 to TIMP-1 mRNA. These findings suggest that ovalitenin A may reduce CCA metastasis, possibly by altering PI3K signaling and its downstream molecular effectors.
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