PT - JOURNAL ARTICLE AU - JR-KAI CHEN AU - SHU-FEN PENG AU - KUANG CHI LAI AU - HSIN-CHUNG LIU AU - YI-PING HUANG AU - CHIN-CHUNG LIN AU - AN-CHENG HUANG AU - FU-SHIN CHUEH AU - JING-GUNG CHUNG TI - Fisetin Suppresses Human Osteosarcoma U-2 OS Cell Migration and Invasion <em>via</em> Affecting FAK, uPA and NF-ĸB Signaling Pathway <em>In Vitro</em> AID - 10.21873/invivo.11542 DP - 2019 May 01 TA - In Vivo PG - 801--810 VI - 33 IP - 3 4099 - http://iv.iiarjournals.org/content/33/3/801.short 4100 - http://iv.iiarjournals.org/content/33/3/801.full SO - In Vivo2019 May 01; 33 AB - Background/Aim: Evidence has indicated that fisetin induces cytotoxic effects in human cancer cell lines, including the inhibition of cell migration and invasion, however, the exact molecular mechanism of action of fisetin in human osteosarcoma cells remains unclear. Materials and Methods: The anti-metastatic mechanisms of fisetin in human osteosarcoma U-2 OS cells were investigated in vitro. Results: Fisetin reduced the viability of cells at different concentrations (2.5, 5 and 10 μM) as measured by flow cytometric assay. Fisetin suppressed cell mobility, migration and invasion of U-2 OS cells, as shown by wound healing assay and transwell filter chambers, respectively. The gelatin zymography assay showed that fisetin inhibited MMP-2 activity in U-2 OS cells. Results from western blotting indicated that fisetin reduced the levels of pEGFR, SOS-1, GRB2, Ras, PKC, p-ERK1/2, p-JNK, p-p-38, VEGF, FAK, RhoA, PI3K, p-AKT, NF-ĸB, uPA, MMP-7, MMP-9, and MMP-13, but increased GSK3β and E-cadherin in U-2 OS cells after 48 h of treatment. Conclusion: Fisetin can be used in the future, as a target for the treatment of metastasis of human osteosarcoma cells.