Adenovirus armed with VGLL4 selectively kills hepatocellular carcinoma with G2/M phase arrest and apoptosis promotion
Adenovirus armed with VGLL4 selectively kills hepatocellular carcinoma with G2/M phase arrest and apoptosis promotion
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携带VGLL4的腺病毒选择性杀死肝细胞癌，并阻滞G2/M期并促进细胞凋亡
DOI：
10.1016/j.bbrc.2018.08.036
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发表时间：
2018-09-18
影响因子：
3.1
通讯作者：
Liu, Xinyuan
中科院分区：
文献类型：
--
作者：
Xie, Wenjie;Hao, Jiali;Liu, Xinyuan
VGLL 4是一种天然的细胞增殖抑制剂，通过多种信号传导途径抑制肿瘤生长。我们首次发现VGLL 4在肝细胞癌（HCC）细胞中引起G2/M期阻滞。然后，我们设计了一种新的携带VGLL 4基因的存活素调节的溶瘤腺病毒Ad-sp-VGLL 4。Ad-sp-VGLL 4具有较高的肝癌靶向选择性，但对正常细胞的伤害较小。该腺病毒构建物由于G2/M期阻滞和增强细胞凋亡而增强抗肿瘤活性。体内实验表明，Ad-sp-VGLL 4对肝癌移植瘤的生长有明显的抑制作用。综上所述，我们的研究结果表明，Ad-sp-VGLL 4具有很强的抗肿瘤能力，在肝癌治疗中有很大的应用潜力。(C)2018爱思唯尔公司All rights reserved.
The Vestigial-Like Family Member 4 (VGLL4) functions as a native inhibitor of cell proliferation and tumor growth through multiple signaling pathways. We first discovered that VGLL4 causes G2/M phase arrest in hepatocellular carcinoma (HCC) cells. Then, we designed a novel survivin-regulated oncolytic adenovirus Ad-sp-VGLL4 carrying the VGLL4 gene. Ad-sp-VGLL4 exerted high HCC-targeting-selectivity but is less harmful to normal cells. This adenovirus construction enhanced antitumor activity due to G2/M phase arrest and enhanced apoptosis. It's also indicated that Ad-sp-VGLL4 could suppress the growth of transplanted tumor of HCC in vivo experiment. Taken together, our results suggest that Ad-sp-VGLL4 possesses strong antitumor capacity and has great potential use for HCC therapy. (C) 2018 Elsevier Inc. All rights reserved.