STAT3 knockdown reduces pancreatic cancer cell invasiveness and matrix metalloproteinase-7 expression in nude mice.
STAT3 knockdown reduces pancreatic cancer cell invasiveness and matrix metalloproteinase-7 expression in nude mice.
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DOI：
10.1371/journal.pone.0025941
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Qiu Zj
中科院分区：
文献类型：
--
作者：
Li Hd;Huang C;Huang Kj;Wu Wd;Jiang T;Cao J;Feng Zz;Qiu Zj
转录激活因子3（Transducer and activator of transcription-3，STAT 3）在肿瘤细胞的侵袭和转移中起重要作用。本研究的目的是研究STAT 3基因敲低对胰腺癌细胞裸鼠移植瘤及其相关基因表达的影响。构建STAT 3 shRNA慢病毒载体，感染SW 1990细胞。采用qRT-PCR和western免疫印迹法检测基因表达。裸小鼠异种移植试验用于评估这些稳定细胞在体内的表型变化。HE染色检测肿瘤细胞侵袭能力，免疫组化检测基因表达。与对照细胞相比，STAT 3 shRNA成功地沉默了SW 1990细胞中STAT 3 mRNA和蛋白的表达。与对照载体肿瘤和亲本细胞产生的肿瘤相比，STAT 3沉默的肿瘤细胞在裸鼠中的生长速率显著降低。与对照组相比，在STAT 3沉默的肿瘤中，肿瘤侵入血管和肌肉也受到抑制。IV型胶原在STAT 3沉默的SW 1990细胞的肿瘤周围是完整和连续的，而IV型胶原在对照肿瘤周围是不完整和不连续的。此外，STAT 3沉默的肿瘤中的微血管密度显著低于SW 1990细胞的亲本或对照肿瘤。此外，与亲本SW 1990异种移植物和对照相比，STAT 3沉默的肿瘤中MMP-7表达降低。相反，IL-1β和IgT 7 α的表达没有改变。这些数据清楚地表明，STAT 3在调节肿瘤生长、侵袭和血管生成中起重要作用，这可能通过降低胰腺癌细胞中MMP-7的表达而起作用。
Transducer and activator of transcription-3 (STAT3) plays an important role in tumor cell invasion and metastasis. The aim of the present study was to investigate the effects of STAT3 knockdown in nude mouse xenografts of pancreatic cancer cells and underlying gene expression. A STAT3 shRNA lentiviral vector was constructed and infected into SW1990 cells. qRT-PCR and western immunoblot were performed to detect gene expression. Nude mouse xenograft assays were used to assess changes in phenotypes of these stable cells in vivo. HE staining was utilized to evaluate tumor cell invasion and immunohistochemistry was performed to analyze gene expression. STAT3 shRNA successfully silenced expression of STAT3 mRNA and protein in SW1990 cells compared to control cells. Growth rate of the STAT3-silenced tumor cells in nude mice was significantly reduced compared to in the control vector tumors and parental cells-generated tumors. Tumor invasion into the vessel and muscle were also suppressed in the STAT3-silenced tumors compared to controls. Collagen IV expression was complete and continuous surrounding the tumors of STAT3-silenced SW1990 cells, whereas collagen IV expression was incomplete and discontinuous surrounding the control tumors. Moreover, microvessel density was significantly lower in STAT3-silenced tumors than parental or control tumors of SW1990 cells. In addition, MMP-7 expression was reduced in STAT3-silenced tumors compared to parental SW1990 xenografts and controls. In contrast, expression of IL-1β and IgT7α was not altered. These data clearly demonstrate that STAT3 plays an important role in regulation of tumor growth, invasion, and angiogenesis, which could be act by reducing MMP-7 expression in pancreatic cancer cells.
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影响因子：
5.7
作者：
Nagai, Shuntaro;Nakamura, Masafumi;Katano, Mitsuo
通讯作者：
Katano, Mitsuo
SRC激酶和表皮生长因子受体与吉西他滨的结合阻断了STAT3介导的胰腺肿瘤生长抑制的耐药性。
DOI：
10.1158/1078-0432.ccr-10-1670
发表时间：
2011-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Nagaraj NS;Washington MK;Merchant NB
通讯作者：
Merchant NB
影响因子：
8
作者：
Niu, GL;Wright, KL;Yu, H
通讯作者：
Yu, H
影响因子：
11.2
作者：
Qu P;Du H;Wang X;Yan C
通讯作者：
Yan C
DOI：
10.1186/1756-9966-29-51
发表时间：
2010-05-19
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Huang C;Yang G;Jiang T;Huang K;Cao J;Qiu Z
通讯作者：
Qiu Z