Mechanism of vascular endothelial growth factor expression mediated by cisplatin in human ovarian cancer cells.
Mechanism of vascular endothelial growth factor expression mediated by cisplatin in human ovarian cancer cells.
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顺铂介导人卵巢癌细胞中血管内皮生长因子表达的机制。
DOI：
10.1016/j.bbrc.2007.04.083
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发表时间：
2007
影响因子：
3.1
通讯作者：
Jiang,Bing-Hua
中科院分区：
文献类型：
--
作者：
Zhong,Xiao-Song;Liu,Ling-Zhi;Skinner,HeathD;Cao,Zongxian;Ding,Min;Jiang,Bing-Hua
顺铂（CDDP）及其类似物广泛用于治疗各种人类实体瘤。然而，其作用的分子机制仍有待了解。血管内皮生长因子（VEGF）是一种有效的血管生成诱导剂，在许多人类癌症中上调。在这项研究中，我们证明了CDDP抑制人卵巢癌细胞中VEGF的表达。我们发现CDDP以剂量依赖性方式抑制VEGF报告基因活性，表明CDDP抑制VEGF的转录激活。我们还发现：（1）在卵巢癌细胞中，由含有突变的HIF-1结合位点的VEGF报道基因介导的荧光素酶活性远低于含有野生型HIF-1结合位点的报道基因的荧光素酶活性，从而证实HIF-1是VEGF表达的主要转录调节因子;和（2）CDDP极大地抑制含有野生型而不是突变的HIF-1结合位点的VEGF报道基因活性。该结果表明，CDDP通过降低HIF-1活性特异性地抑制VEGF转录激活。共转染HIF-1的显性阴性构建体抑制卵巢癌细胞中VEGF报告基因活性。CDDP特异性地通过HIF-1α的表达而不是通过HIF-1β的表达来抑制VEGF转录激活。我们证明了VEGF受体KDR在卵巢癌细胞中表达，CDDP抑制的VEGF表达与细胞凋亡有关，VEGF治疗可挽救细胞凋亡。这些结果提示CDDP通过HIF-1表达和VEGF转录激活在卵巢癌细胞中的抗肿瘤活性的新机制。
Cisplatin (CDDP) and its analogues are widely used for the treatment of a variety of human solid tumors. However, the molecular mechanism of its action remains to be understood. Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and is upregulated in many human cancers. In this study we demonstrated that CDDP-inhibited VEGF expression in human ovarian cancer cells. We found that CDDP inhibited the VEGF reporter activity in a dose-dependent manner, indicating that CDDP-inhibited transcriptional activation of VEGF. We also found that: (1) luciferase activity mediated by the VEGF reporter containing a mutation of the HIF-1 binding site was much lower than that of the reporter containing a wild-type HIF-1 binding site in ovarian cancer cells, thus confirming that HIF-1 is a major transcriptional regulator of VEGF expression; and that (2) CDDP greatly inhibited VEGF reporter activity containing the wild-type but not the mutant HIF-1 binding site. This result indicates that CDDP-inhibited VEGF transcriptional activation specifically by decreasing HIF-1 activity. Co-transfection of a dominant negative construct of HIF-1 inhibited VEGF reporter activity in ovarian cancer cells. CDDP-inhibited VEGF transcriptional activation specifically through the expression of HIF-1α, but not HIF-1β. We demonstrated that VEGF receptor KDR was expressed in ovarian cancer cells, and that CDDP-inhibited VEGF expression was linked with cellular apoptosis, which was rescued by VEGF treatment. These results suggest a novel mechanism of CDDP’s anti-tumor activity in ovarian cancer cells via HIF-1 expression and VEGF transcriptional activation.
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影响因子：
11.2
作者：
M. Selvakumaran;Debra A Pisarcik;R. Bao;A. Yeung;T. C. Hamilton
通讯作者：
M. Selvakumaran;Debra A Pisarcik;R. Bao;A. Yeung;T. C. Hamilton
影响因子：
11.2
作者：
M. Prewett;James Huber;L. Yiwen;Angel Santiago;W. O'Connor;K. King;J. Overholser;A. Hooper;B. Pytowski;L. Witte;P. Bőhlen;D. Hicklin
通讯作者：
M. Prewett;James Huber;L. Yiwen;Angel Santiago;W. O'Connor;K. King;J. Overholser;A. Hooper;B. Pytowski;L. Witte;P. Bőhlen;D. Hicklin
DOI：
10.1111/j.1749-6632.1997.tb52002.x
发表时间：
1997-01-01
期刊：
ATHEROSCLEROSIS IV: RECENT ADVANCES IN ATHEROSCLEROSIS RESEARCH
影响因子：
--
作者：
Carmeliet, P;Moons, L;Collen, D
通讯作者：
Collen, D
DOI：
10.1152/ajpcell.1996.271.4.c1172
发表时间：
1996-10-01
影响因子：
5.5
作者：
Jiang, BH;Semenza, GL;Marti, HH
通讯作者：
Marti, HH
DOI：
10.1200/jco.2003.01.066
发表时间：
2003
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
W. Mcguire
通讯作者：
W. Mcguire