Inhibition of perillyl alcohol on cell invasion and migration depends on the Notch signaling pathway in hepatoma cells
Inhibition of perillyl alcohol on cell invasion and migration depends on the Notch signaling pathway in hepatoma cells
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DOI：
10.1007/s11010-015-2593-x
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发表时间：
2016-01-01
影响因子：
4.3
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Ma, Yong;Bian, Jianmin;Zhang, Feng
细胞转移，特别是侵袭和迁移过程，被认为是导致肝细胞癌（HCC）高死亡率的主要原因，HCC已成为全球第六大常见癌症和第三大癌症死亡原因。在本研究中，我们旨在探索紫苏醇对肝癌细胞侵袭和迁移的影响及其潜在的分子机制。transwell实验结果显示，肝癌细胞（HepG2、SMMC-7721和MHCC97H）的细胞侵袭性和迁移能力明显高于正常肝细胞（HL-7702），紫薇醇处理后细胞侵袭性和迁移能力显著降低（P < 0.05）。实时逆转录聚合酶链反应（RT-PCR）检测的Notch信号通路下游靶基因HES1、HES5、HEY1 mRNA表达水平在肝癌细胞中显著升高（P < 0.05）。紫苏醇处理后，肝癌细胞中这些mRNA水平显著降低（P < 0.05）。此外，与正常肝细胞相比，肝癌细胞Notch1胞内结构域（N1ICD）和Snail蛋白表达水平显著升高，E-cadherin蛋白表达水平显著降低（P < 0.05）。紫苏叶醇显著降低了肝癌细胞N1ICD和Snail蛋白的表达，提高了E-cadherin蛋白的表达（P < 0.05）。综上所述，紫苏醇可能通过降低Notch信号通路活性，增加蜗牛调节的E-cadherin表达，在肝癌细胞侵袭迁移过程中发挥重要作用。
Cell metastasis, especially the process of invasion and migration, is considered as the main cause for the high mortality rate of hepatocellular carcinoma (HCC), which has become the sixth most common cancer worldwide and the third leading cause of cancer death. In this present study, we aimed to exploit the effects of perillyl alcohol on cell invasion and migration and the underlying molecular mechanisms in HCC. According to the transwell assays, cell invasiveness and migratory capacity were markedly higher in hepatoma cells (HepG2, SMMC-7721 and MHCC97H) than those in normal liver cells (HL-7702), and then significantly suppressed by perillyl alcohol treatment (P < 0.05). Meanwhile, the mRNA levels of Notch signaling pathway downstream target genes, HES1, HES5, and HEY1, were notably higher in hepatoma cells detected with real-time reverse transcription polymerase chain reaction (RT-PCR) (P < 0.05). After treated with perillyl alcohol, these mRNA levels were significantly decreased in hepatoma cells (P < 0.05). In addition, compared with the normal liver cells, the protein expression levels of Notch1 intracellular domain (N1ICD) and Snail were significantly increased, while E-cadherin protein expression was significantly decreased in hepatoma cells (P < 0.05). However, perillyl alcohol treatment significantly decreased N1ICD and Snail protein expressions and increased E-cadherin protein expression in hepatoma cells (P < 0.05). In conclusion, perillyl alcohol might play an important role in the process of hepatoma cell invasion and migration via decreasing the activity of Notch signaling pathway and increasing E-cadherin expression regulated by Snail.