WW domain containing oxidoreductase induces apoptosis in gallbladder-derived malignant cell by upregulating expression of P73 and PUMA
WW domain containing oxidoreductase induces apoptosis in gallbladder-derived malignant cell by upregulating expression of P73 and PUMA
复制标题
含有WW结构域的氧化还原酶通过上调P73和PUMA的表达诱导胆囊源性恶性细胞凋亡
DOI：
10.1007/s13277-013-1213-1
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
王琳
中科院分区：
文献类型：
--
作者：
王琳
胆囊癌（GBC）是全球癌症相关死亡的主要原因之一。含WW结构域的氧化还原酶（WWOX）是一种抑癌基因，可抑制多种肿瘤的增殖。然而，人们对WWOX与胆囊癌之间的关系知之甚少。本研究旨在研究WWOX对胆囊恶性肿瘤细胞的体内外抑瘤作用，并探讨其潜在的肿瘤毒作用机制。结果表明，WWOX可诱导GBC细胞凋亡，并使胞浆中P73和P450 A的表达增加。我们还发现，Bax已上调后，WWOX过表达，而Bcl-2下调WWOX。为了进一步验证体内结果，我们评估了WWOX在胆囊癌小鼠模型中的肿瘤抑制作用。结果表明，WWOX可抑制肿瘤细胞的增殖，并上调靶组织中P73和P74 A的表达。与阴性对照组相比，给予WWOX的小鼠模型显示出更好的预后。本研究结果表明，WWOX可作为胆囊癌基因治疗的治疗剂。
Gallbladder cancer (GBC) is one leading cause of cancer-related death worldwide. WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene which can suppress proliferation of a variety of tumors. However, little was known about the relationships between WWOX and gallbladder cancer. In the current study, we intended to investigate the tumor suppressive role of WWOX in gallbladder malignant cells both in vitro and in vivo, and explore the potential mechanism of tumor toxic function of WWOX. Our results have shown that WWOX triggerred apoptosis in GBC cells and increased the expression of P73 and PUMA in cytoplasm. We also have found that Bax has been upregulated after overexpression of WWOX, whereas, Bcl-2 was downregulated by WWOX. To further validate the results in vivo, we evaluated the tumor suppressive role of WWOX in mouse model of gallbladder cancer. The results have shown that the proliferation of the tumor was inhibited after delivery of WWOX, and the expressions of P73 and PUMA were upregulated in target tissues. The mice models administrated with WWOX have shown better prognosis than mice in negative control groups. The results from our study indicated that WWOX could be used as a therapeutic agent in the gene therapy of gallbladder cancer.
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DOI：
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DOI：
10.1111/j.1440-1746.2011.07048.x
发表时间：
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影响因子：
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作者：
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