Baicalein inhibits tumor migration in highly invasive non-small-cell lung cancer cells

• Main Authors: Wan-Jiun Chen, 陳菀均
• Other Authors: Huei-Wen Chen
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/08900641341482917588

碩士 === 國立陽明大學 === 藥理學研究所 === 96 === To inhibit metastasis, prolong survival, with an emphasis on restricting treatment-related toxicity are the key points in new drug development for anti-cancer therapy. Herein we report that baicalein, a selective inhibitor of 12-lipoxygenase, inhibited cancer cell migration (51.87% of inhibition at 5 microM) and invasion (50.6% of inhibition at 5 microM) concentration-dependently at sub-lethal concentration (1-5 microM) using would-healing analysis and Transwell system in the highly invasive human lung adenocacinoma cell line (CL1-5). According to the Affymetrix chip assay, the gene expression profiles of baicalein treatment showed that several metastasis-related genes were highly regulated by baicalein. The real time quantitative RT-PCR confirmed that the cell adhesion molecules: integrin alphav (2.74 folds increased) alpha6 (3.46 folds increased), and beta1 (4.19 folds increased�w were significantly regulated by baicalein. Immunostaining and flow cytometry also showed the induction of integrin alpha6 1.55 folds increased integrin beta1�v2.8 folds increased in protein levels on the baicalein-treated groups. Further studies demonstrated that the cell adhesion ability to fibronectin was increased by baicalein (4.68 folds of induction at 5 microM) through inducing integrin expression in CL1-5 cells. Pathway analysis showed that baicalein exhibited the effects to down-regulate some cell motility related genes (keratin 19, cytokeratin II, CDC42 effector protein 1, 5, and Rac/cdc42 exchanger factor) and at least two cell invasion-related serine proteases (prss2, and prss3). Interestingly, the major regulators of the cell motility signaling pathway, RhoGTPase activating proteins (RhoGAPs), were up-regulated by baicalein, which might lead to reduce RhoA activation and inhibit translocation of cell body. Upon on these results, we suggested that baicalein could be a novel anti-cancer drug with the potential to inhibit cancer cell invasion and migration through up-regulating integrin alpha6beta1 expression to enhance cell adhesion and increasing RhoGAPs to inhibit the RhoA GTP pathway to reduce cell migration in the highly invasive lung adenocarcinoma cells.