关键词: 异硫氰酸苯乙酯, 基质金属蛋白酶9, 核转录因子κB

Abstract: Objective To investigated the anti-invasive mechanisms of PEITC in human colon cancer SW480 cells. Methods Human colon cancer SW480 cell line was cultured in vitro, and treated with 10, 30,50μmol/L PEITC for 24h. Cell viability, cell migration and invasion was analyzed by MTT assay, scratch healing assay and transwell membrane assay, respectably. Activity of Matrix metalloproteinase-9 (MMP-9) was analyzed by a fluorescence resonance energy transfer kits, and MMP-9 mRNA expression was detected by RT-PCR. Activation of phosphoinisitide-3-kinase (PI3K) /Akt/mammalian target of rapamycin (mTOR) and phosphatase and tensin homologue (PTEN), and nuclear translocation of nuclear factor kappa B (NF-κB) were examined by Western blot. NF-κB activity was detected by luciferase reporter assay. Furthermore, a mice model with xenograft tumors was constructed, and the effect of PEITC on tumor growth was analyzed. Results PEITC significantly reduced SW480 cells invasion and migration without affecting the viability of cells (P<0.05). PEITC also markedly inhibited MMP-9 activity and expression at both protein and mRNA levels (P<0.05). PEITC attenuated PI3K and phosphorylation of AKT and mTOR, whereas PTEN was increased. In the meantime, PEITC inhibited NF-κB transcriptional activity (P<0.05). In addition, PEITC diminished NF-κB nuclear translocation. Furthermore, PEITC could significantly inhibit xenograft tumors growth in nude mice (P<0.05). Conclusion PEITC as a potential anti-invasive agent by inhibiting MMP-9 involved in PI3K/AKT and NF-κB pathways.

Key words: PEITC, MMP-9, NF-kB