Promotive effects of bone morphogenetic protein 2 on angiogenesis in hepatocarcinoma via multiple signal pathways.
Promotive effects of bone morphogenetic protein 2 on angiogenesis in hepatocarcinoma via multiple signal pathways.
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骨形态发生蛋白2通过多种信号通路对肝癌血管生成的促进作用。
DOI：
10.1038/srep37499
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发表时间：
2016-11-25
影响因子：
4.6
通讯作者：
Wu JB
中科院分区：
文献类型：
--
作者：
Zuo WH;Zeng P;Chen X;Lu YJ;Li A;Wu JB
骨形态发生蛋白2(BMP-2)对肝细胞癌血管生成的影响尚未见报道，其分子机制尚不清楚。我们首先构建了表达针对BMP-2基因的小发夹状RNA的重组慢病毒载体(LV-SH-BMP2)和高表达BMP-2的重组慢病毒载体(过表达-LV-BMP2)，然后将这两个重组慢病毒载体分别导入Hep G2细胞。将转染LV-SH-BMP2和高表达LV-BMP2的Hep G2细胞分别与人脐静脉内皮细胞共培养，观察BMP-2对HUVECs的影响。观察BMP-2对肿瘤微血管密度(MVD)的影响。与BMP-2基因敲除的HEp G2共培养的人脐静脉内皮细胞的增殖、迁移和血管生成能力明显受到抑制(均P 和 0.0 5)，而与BMP-2高表达的HEp G2共培养的人脐静脉内皮细胞的增殖、迁移和血管生成能力明显增强(均P 和 0.0 5)。高表达LV-BMP2转染组Hep G2肿瘤微血管密度显著增加，而LV-SH-BMP2转染组Hep G2肿瘤微血管密度降低。 、p-P38、p-ERK、p-AKT、p-m-TOR蛋白表达在BMP-2过表达后显著增加，而在BMP-2基因敲除后显著降低(P均< )。提示BMP-2可能通过P38、ERK和Akt/m-Tor途径促进HUVEC的增殖、迁移和血管生成。
The effects of Bone morphogenetic protein 2 (BMP-2) on the angiogenesis of hepatocellular carcinoma have not yet been observed and its molecular mechanisms is not clear. We first constructed the recombinant lentivirus vectors expressing small hairpin RNA against BMP-2 gene (LV-SH-BMP2) and the recombinant lentivirus vectors over-expressing BMP-2 (overexpression-LV-BMP2), and then the two recombinant lentivirus vectors were respectively transfected into Hep G2 cells. The Hep G2 cells transfected with LV-SH-BMP2 or overexpression-LV-BMP2 were respectively co-cultured with human umbilical vein endothelial cells (HUVECs) to observe the effects of BMP-2 on HUVECs. The effect of BMP-2 on tumor microvessel density (MVD) was examined. The abilities of proliferation, migration and angiogenesis were significantly inhibited in the HUVECs co-cultured with BMP-2 knockdown Hep G2 (all P < 0.05), but significantly enhanced in the HUVECs co-cultured with BMP-2 overexpression Hep G2 (all P < 0.05). MVD was significantly increased in overexpression-LV-BMP2-transfected Hep G2 tumor, but decreased in LV-SH-BMP2-transfected Hep G2 tumors. The protein expressions of VEGF, p-P38, p-ERK, p-AKT, p-m-TOR were significantly increased after BMP-2 over-expression, or significantly decreased after BMP-2 knockdown (all P < 0.05). These results reveal that BMP-2 can enhance HUVEC proliferation, migration and angiogenesis through P38, ERK and Akt/m-TOR pathway.
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影响因子：
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作者：
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通讯作者：
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影响因子：
5.8
作者：
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通讯作者：
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影响因子：
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通讯作者：
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