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腺病毒表达的线粒体融合蛋白 2 基因在人结直肠癌细胞系中使细胞周期停滞在 G2/M 期并抑制增殖。

Cell-cycle arrest at G2/M and proliferation inhibition by adenovirus-expressed mitofusin-2 gene in human colorectal cancer cell lines.

出版信息

Neoplasma. 2013;60(6):620-6. doi: 10.4149/neo_2013_080.

DOI:10.4149/neo_2013_080
PMID:23906296
Abstract

The mitofusin-2 (Mfn2) is a novel gene characterised as a cell proliferation inhibitor. Mfn2 protein over-expression, mediated by an adenovirus, has a significant anti-proliferative effect in hepatoma carcinoma cells. However, there is no report on the effect of Mfn2 on colorectal cancer (CRC). In this study, we found that Mfn2 protein and mRNA levels were downregulated in CRC tissues compared to nearby normal tissues. An adenovirus encoding the complete Mfn2 open reading frame (Ad-Mfn2) exhibited a prominent anti-proliferative effect in the CRC cell lines HCT 116, HT-29, and SW480. Ad-Mfn2 infection significantly inhibited the proliferation of CRC cells compared with Ad-GFP infection. Mfn2 overexpression resulted in a cell-cycle arrest at G2/M phase in CRC cells, and it increased the levels of p-cdc2 (Tyr15) and Myt1; however, the levels of cyclin B1 and p-ERK1/2 was reduced. Mfn2 overexpression aslo increased the levels of active caspase-3 and cleaved PARP. Taken together, these findings indicate that Mfn2 has a significant anti-proliferative effect in CRC cells using adenoviral vectors.

摘要

线粒体融合蛋白 2(Mfn2)是一种新型基因,被描述为细胞增殖抑制剂。腺病毒介导的 Mfn2 蛋白过表达对肝癌细胞具有显著的抗增殖作用。然而,目前尚无关于 Mfn2 对结直肠癌(CRC)影响的报道。在本研究中,我们发现与邻近正常组织相比,CRC 组织中 Mfn2 蛋白和 mRNA 水平下调。携带完整 Mfn2 开放阅读框的腺病毒(Ad-Mfn2)在 CRC 细胞系 HCT116、HT-29 和 SW480 中表现出显著的抗增殖作用。与 Ad-GFP 感染相比,Ad-Mfn2 感染显著抑制 CRC 细胞的增殖。Mfn2 过表达导致 CRC 细胞周期停滞在 G2/M 期,同时增加了 p-cdc2(Tyr15)和 Myt1 的水平;然而,cyclin B1 和 p-ERK1/2 的水平降低。Mfn2 过表达还增加了活性 caspase-3 和 cleaved PARP 的水平。综上所述,这些发现表明,使用腺病毒载体,Mfn2 对 CRC 细胞具有显著的抗增殖作用。

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