Synergistic effect of resveratrol and HSV-TK/GCV therapy on murine hepatoma cells.
Synergistic effect of resveratrol and HSV-TK/GCV therapy on murine hepatoma cells.
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白藜芦醇与HSV-TK/GCV治疗对小鼠肝癌细胞的协同作用
DOI：
10.1080/15384047.2018.1523094
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发表时间：
2019
影响因子：
3.6
通讯作者：
Du B
中科院分区：
文献类型：
--
作者：
Xiao J;Wang X;Wu Y;Zhao Q;Liu X;Zhang G;Zhao Z;Ning Y;Wang K;Tan Y;Du B
尽管转移效率较低，但用HSV-TK进行自杀基因治疗以其旁观者杀伤效应而闻名。基于连接蛋白的间隙连接被认为介导了旁观者效应。最近，我们发现白藜芦醇（一种多酚化合物）可增加小鼠肝癌细胞中连接蛋白Cx26和Cx43的表达，而Cx26和Cx43是缝隙连接的重要成分。假设，白藜芦醇诱导的间隙连接上调可能改善HSV-TK/GCV对肝癌细胞的旁观者效应。本研究表明，白藜芦醇可以增强CBRH7919肝癌细胞间隙连接的细胞间通讯，从而增强GCV对CBRH7919TK细胞的旁观者杀伤作用。然而，使用其长期抑制剂α -甘草次酸抑制间隙连接对HSV-TK/GCV基因治疗的旁观者效应有负面影响。此外，白藜芦醇和GCV以2:3的比例联合处理CBRH7919TK和CBRH7919WT细胞的荷瘤小鼠，与GCV或单独白藜芦醇相比，肿瘤的体积和重量明显减少。结果表明，白藜芦醇可以通过增强连接素介导的间隙连接通讯来增强HSV-TK/GCV系统的旁观者效应。
ABSTRACT Despite its low transfer efficiency, suicide gene therapy with HSV-TK is known for its bystander killing effect. The connexin-based gap junction is believed to mediate the bystander effect. Recently, we found that resveratrol, a polyphenol compound, increased the expression of Cx26 and Cx43, which are connexins and important constituents of gap junctions, in murine hepatoma cells. Hypothetically, the resveratrol-induced upregulation of gap junctions may improve the bystander effect that HSV-TK/GCV has on hepatoma cells. Our present investigation revealed that resveratrol could enhance intercellular communication at the gap junctions in CBRH7919 hepatoma cells and thereby enhance the bystander killing effect of GCV on CBRH7919TK cells. However, inhibition of gap junction using its long-term inhibitor alpha-glycyrrhetinic acid had a negative influence on the bystander effect of gene therapy with HSV-TK/GCV. In addition, combined resveratrol and GCV treatment in tumor-bearing mice with CBRH7919TK and CBRH7919WT cells at a ratio of 2:3 resulted in a significant decrease in the volume and weight of the tumor in comparison to GCV or only resveratrol. The present results demonstrate that resveratrol can enhance the bystander effect exerted by the HSV-TK/GCV system by enhancing connexin-mediated gap junctional communication.
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影响因子：
16.1
作者：
Karjoo Z;Chen X;Hatefi A
通讯作者：
Hatefi A
影响因子：
56.9
作者：
SIMPSON, I;ROSE, B;LOEWENSTEIN, WR
通讯作者：
LOEWENSTEIN, WR
影响因子：
5.1
作者：
van der Eb, MM;Cramer, SJ;Hoeben, RC
通讯作者：
Hoeben, RC
影响因子：
62.1
作者：
Du X;Zhou J;Shi J;Xu B
通讯作者：
Xu B
DOI：
10.3390/molecules22030474
发表时间：
2017-03-16
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Nivelle L;Hubert J;Courot E;Jeandet P;Aziz A;Nuzillard JM;Renault JH;Clément C;Martiny L;Delmas D;Tarpin M
通讯作者：
Tarpin M