Rab23 is a potential biological target for treating hepatocellular carcinoma

Rab23 is a potential biological target for treating hepatocellular carcinoma
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DOI:
10.3748/wjg.v13.i7.1010
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发表时间:
2007-02-21
影响因子:
4.3
通讯作者:
Zhang, Hong-Wei
Zhang, Hong-Wei
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Yun-Jian;Wang, Qian;Zhang, Hong-Wei

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目的:通过评估 Rab23 在 HCC 组织和 HCC 细胞系中的表达,阐明 Rab23 在肝细胞癌 (HCC) 中的作用。 方法:采用免疫组织化学和组织微阵列原位杂交技术,用 Rab23 抗体对原发性肿瘤 (n = 100) 进行染色。分析基因表达与病理参数之间的关系。通过敲除 Rab23 基因表达来检查 Rab23 在 Hep-3B 细胞中的生物学意义。我们设计了一对针对人 rab23 的双链 RNA,并将 siRNA 转染到 Hep-3B 细胞中。使用 RT-PCR 和蛋白质印迹检查这些细胞中的 Rab23 表达。我们通过 MTT 测定和荧光激活细胞分选研究了细胞生长。 结果:71 名 HCC 患者中的 38 名 (53.5%) 和 68 名 HCC 患者中的 49 名 (72%) 分别发现 Rab23 高细胞质和核表达,这与肿瘤大小相关。 HCC 细胞系表达 Rab23。在 Hep3B 细胞中,Rab23 的 siRNA 使 Rab23 mRNA 降低 4.5 倍,蛋白质表达降低 2 倍。转染siRNA的Hep-3B细胞在24和48小时的存活率较低,约30%的Hep-3B细胞凋亡。敲除 rab23 可抑制 Hep3B 细胞生长,表明 rab23 在 Hep3B 细胞生长中发挥重要作用。结论:Rab23 在 HCC 中过度表达和/或激活。 Rab23 可能既是 HCC 预测因子,又是治疗 HCC 的靶标。 (c) 2007 年 WIG 出版社。版权所有。
AIM: To elucidate the role of Rab23 in hepatocellular carcinoma (HCC) by assessing the expression of Rab23 in HCC tissue and in HCC cell lines.METHODS: Primary tumors (n = 100) were stained with Rab23 antibodies using immunohistochemistry and in situ hybridization in tissue microarrays. Relationships between gene expression and pathology parameters were analysed. The biological significance of Rab23 in Hep-3B cells was examined by knocking down Rab23 gene expression. We designed a pair of double-stranded RNAs against human rab23 and transfected siRNA into Hep-3B cells. Rab23 expression in these cells was examined using RT-PCR and Western blots. We investigated cell growth by MTT assays and fluorescence-activated cell sorting.RESULTS: High cytoplasmic and nuclear expression of Rab23 was found in 38 of 71 (53.5%) and in 49 of 68 HCC patients (72%) respectively, which correlated with tumor size. HCC cell lines expressed Rab23. In Hep3B cells, siRNA for Rab23 decreased Rab23 mRNA by 4.5-fold and protein expression by 2-fold. Survival rates at 24 and 48 h for Hep-3B cells transfected with siRNA were lower and about 30% Hep-3B cells were apoptotic. Knocking down rab23 suppressed Hep3B cell growth, suggesting that rab23 could play an important role in Hep3B cell growth.CONCLUSION: Rab23 is overexpressed and/or activated in HCC. Rab23 may be both a HCC predictor and a target for treating HCC. (c) 2007 The WIG Press. All rights reserved.