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Role of PKCβ in hepatocellular carcinoma cells migration and invasion in vitro: a potential therapeutic target

机译:PKCβ在肝癌细胞体外迁移和侵袭中的作用:潜在的治疗靶点

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摘要

Considerable interests have recently been focused on mechanism of human hepatocellular carcinoma (HCC) metastasis—the most fundamental characteristics of HCC and the ultimate cause of most HCC mortality, so screening more potential early prognostic marker and therapeutic target is urgent. In this study, we screened genome of three HCC cell lines with consistently increased metastatic potentials and sharing same genetic background, through DNA microarray and found consecutively up-regulated expression of PKCβ in these cell lines compared to others PKCs, which was reconfirmed by real time RT-PCR and western blot analysis. Moreover, it was found, after efficient silence of PKCβ by RNAi assay or inhibition of PKCβ activity by a specific inhibitor LY317615, migration and invasion of HCC cells significantly decreased. In addition, depletion of PKCβ protein significantly reversed the enhancement of PMA-stimulated HCC migration and invasion ability in vitro. All the data suggest a key role of PKCβ in HCC motility and PKCβ may be a potential therapeutic target.
机译:最近,人们非常关注人类肝细胞癌(HCC)转移的机制-HCC的最基本特征和大多数HCC死亡的最终原因,因此迫切需要筛选更多潜在的早期预后标志物和治疗靶标。在这项研究中,我们通过DNA微阵列筛选了三种转移性潜能不断提高且具有相同遗传背景的HCC细胞基因组,发现与其他PKC相比,这些细胞系中PKCβ的表达连续上调,这已得到实时证实。 RT-PCR和蛋白质印迹分析。此外,发现在通过RNAi测定有效沉默PKCβ或通过特异性抑制剂LY317615抑制PKCβ活性后,HCC细胞的迁移和侵袭显着降低。此外,PKCβ蛋白的耗竭显着逆转了PMA刺激的HCC迁移和体外侵袭能力的增强。所有数据表明PKCβ在肝癌运动中起关键作用,而PKCβ可能是潜在的治疗靶标。

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