论文部分内容阅读
目的:近年来许多研究显示,摄取较多富含茄红素的食物可降低摄护腺癌以及肝癌的发生率.虽然茄红素被证实具有抑制癌症转移的能力,但目前为止其作用机制仍不清楚.因此,本研究的主要目的在于探讨茄红素的抗癌转移作用及机制.我们提出的假说为:茄红素具有抑制癌转移的能力,其机制可能与调降基质金属蛋白酶-9(matrix metalloproteinase-9;MMP-9)的表现有关.试验方法:将高侵袭能力的肝癌细胞株SK-Hep-1以茄红素预培养2 h,以磷酸盐类缓冲溶液清洗后并继续培养24 h,之后进行各种分析,包括:以transwell分析癌细胞侵袭能力;以同功酵素图谱(zymography)及西方墨点法个别分析MMP-9的酵素活性及蛋白表现;另外,利用电泳移动偏移分析(electrophoretic mobility shift assay;EMSA)检测转录因子NF-kB、AP-1以及Spl对MMP-9启动子(promoter)的结合能力.结果:茄红素具有抑制肝癌细胞侵袭的能力,而抑制效果与剂量关系呈钟型曲线,亦即以5 mmol/L剂量的抑制效果最好(抑制率达63%,P＜0.001);同时,在抑制MMP-9的活性及蛋白表现上也呈相同趋势.此外,茄红素也会降低转录因子NF-kB及Sp1对MM-9启动子的结合能力.结论:茄红素具有抑制癌细胞侵袭的能力,其机制可能与降低转录因子NF-kB和Sp1结合至MMP-9启动子的能力以及减少MMP-9蛋白的表现有关.本研究增加了对茄红素抑制癌转移作用机制的了解,将有助于茄红素作为保健食品上的实用基础.“,”Aims: The carotenoid lycopene, rich in tomatoes, has been associated with decreased risks of several types of cancer, such as prostate cancer and hepatoma. Although lycopene has been shown to inhibit metastasis, the mechanism is poorly understood. In this study, we investigated the mechanisms of anti-metastatic effects of lycopene. We hypothesized that lycopene may inhibit cancer cell invasion via down-regulating the expression of matrix metalloproteinase (MMP) -9. Methods:We tested the inhibitory activity of lycopene on MMP-9 in a highly invasive human hepatoma, SK-Hep-1 cells. MMP-9 activity and expression were detected by gelatin zymography and western blotting, respectively. The binding abilities of nuclear factor-kappa B (NF-kB), activator protein-1 (AP-1) and stimulatory protein-1 (Sp-1) to the binding sites in the MMP-9promoter, which is known to play a crucial role for MMP-9 expression, were also exammed by the electrophoretic mobility shift assay (EMSA) . Resulst: Lycopene inhibited SK-Hep-1 invasion in a bell-shaped manner that was correlated with the expression of MMP-9 protein and protein activity. Furthermore, lycopene significantly inhibited the binding abilities of transcription factors NF-kB and SP-1. Conclusions: Lycopene decreases the invasive ability of SK-Hep-1 cells possibly by reducing MMP-9 expression and suppressing the binding activity of NF-kB and SP-1. By elucidating the possible mechanism (s) underlying the anti-invasive action of lycopene, the present results provide solid academic suggest for its use as an anti-cancer agent.