Inhibition of STAT3 by RNA interference suppresses angiogenesis in colorectal carcinoma

Qian, Wenwei; Guan, Wenxian; Gao, Yong; Tan, Jingxue; Qiao, Zhiqiang; Huang, Huaxing; Xia, Cong

doi:10.1590/s0100-879x2011007500143

Cited by 20 publications

(22 citation statements)

References 34 publications

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“…The mechanisms by which Stat3 may promote tumor metastasis remain poorly understood, but it has been shown that Stat3 can target different downstream genes in different tumors, such as the antiapoptotic gene XIP in B cell leukemia [33], VEGF in diverse human cancers [34], MMP2 in melanoma, and paxillin in ovarian cancer [35][36][37]. Our data demonstrated that MMP2 was simultaneously over-expressed with p-Stat3 in the ESCC with lymph node metastasis when compared with that in the ESCC without lymph node metastasis.…”

Section: Discussionmentioning

confidence: 99%

Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2

Xuan

Lou

et al. 2014

Mol Biol Rep

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Stat3 alters the expression of its downstream genes and is associated with tumor invasion and metastasis in several human cancers. Its role in esophageal squamous cell carcinoma (ESCC) has not been well characterized. We examined the tumor sections of 100 cases of ESCC by immunohistochemistry and observed significant overexpression of Stat3 in the cytoplasm of 89% of ESCC cells and of phosphorylated Stat3 (p-Stat3) in the nuclei of 71% of ESCC when compare with normal esophageal mucosa (72%, p = 0.02; and 31%, p = 0.001). Overexpression of Stat3 and p-Stat3 positively correlated with that of matrix metalloproteinase-2 (MMP2), a known regulator for cell migration, in 65% of ESCC while only 26% shown in benign esophageal mucosa. To further investigate the association of Stat3 with tumor metastasis in vitro, invasion of EC-1 cells (a human ESCC cell line) were investigated with Boyden chambers. The results showed that transfection of Stat3 not only promoted invasion of EC-1 cells but also significantly induced MMP2 expression in a dose-dependent manner. In contrast, suppressing expression of endogenous Stat3 mRNA and protein by Stat3 siRNA significantly reduced EC-1 cell invasion and MMP2 expression. A high-affinity Stat3-binding element was localized to the positions of 648-641 bp (TTCTCGAA) in the MMP2 promoter with electrophoretic mobility shift assay. Our results suggest that Stat3, p-Stat3, and MMP2 were overexpressed in ESCC and associated with invasion of ESCC; and Stat3 up-regulated expression of MMP2 in ESCC through directly binding to the MMP2 promoter.

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Section: Discussionmentioning

confidence: 99%

Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2

Xuan

Lou

et al. 2014

Mol Biol Rep

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“…In our previous research, STAT3 was increased in the HT-29 cell line, one colorectal cancer cell line, and regulated the cell growth and cell cycle [14]. Given the role of cyclinD1 in the cell cycle, the finding that STAT3 regulated the cell growth and the bioinformatics analysis, it may be proposed that STAT3 regulate the expression of cyclinD1 by targeting its binding sites in the promoter of cyclinD1 to control the cell growth.…”

Section: Introductionmentioning

confidence: 96%

Inhibition of STAT3/cyclinD1 pathway promotes chemotherapeutic sensitivity of colorectal caner

Qin

Gao

et al. 2015

Biochemical and Biophysical Research Communications

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“…The process of angiogenesis is highly regulated by multiple cellular signaling transduction pathways including signal transducer and activator of transcription 3 (STAT3), serinethreonine kinase Akt and mitogen-activated protein kinases (10)(11)(12)(13)(14). Aberrant activation of these pathways promotes tumor angiogenesis by inducing the expression of numerous critical angiogenic stimulators (15)(16)(17), including vascular endothelial growth factor A (VEGF-A), basic fibroblast growth factor (bFGF) and nitric oxide (NO) (18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Pien Tze Huang inhibits tumor angiogenesis in a mouse model of colorectal cancer via suppression of multiple cellular pathways

et al. 2013

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Abstract. Angiogenesis plays an essential role in cancer progression, which therefore has become an attractive target for anticancer treatment. Tumor angiogenesis is tightly regulated by multiple signaling pathways that usually function redundantly; in addition, crosstalk between these pathways forms a complicated network that is regulated by compensatory mechanisms. Given the complexity of pathogenic mechanisms underlying tumor angiogenesis, most currently used angiogenesis inhibitors that only target single pathways may be insufficient and probably generate drug resistance, thus, increasing the necessity for development of novel anticancer agents. Traditional Chinese medicines (TCM) are receiving great interest since they have relatively fewer sideeffects and have been used for thousands of years to clinically treat various types of diseases including cancer. Pien Tze Huang (PZH), a well-known traditional Chinese formulation that was first prescribed 450 years ago, has long been used as an alternative remedy for cancers. However, the precise mechanism of PZH's anticancer activity remains to be further elucidated. Using a colorectal cancer mouse xenograft model, in the present study, we evaluated the effect of PZH on tumor angiogenesis and investigated the underlying molecular mechanisms. We found that PZH inhibited tumor growth since PZH treatment resulted in decrease in both tumor volume and tumor weight in CRC mice. In addition, PZH suppressed the activation of several signaling pathways such as STAT3, Akt and MAPKs. Consequently, the inhibitory effect of PZH on these pathways resulted in the inhibition of tumor angiogenesis as demonstrated by the decrease of microvessel density in tumor tissues. Moreover, PZH treatment reduced the expression of angiogenic factors including iNOS, eNOS, VEGF-A, bFGF as well as their specific receptors VEGFR2 and bFGFR. Altogether, our findings suggest that inhibition of tumor angiogenesis via suppression of multiple signaling pathways might be one of the mechanisms whereby PZH affects cancers.

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Inhibition of STAT3 by RNA interference suppresses angiogenesis in colorectal carcinoma

Cited by 20 publications

References 34 publications

Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2

Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2

Inhibition of STAT3/cyclinD1 pathway promotes chemotherapeutic sensitivity of colorectal caner

Pien Tze Huang inhibits tumor angiogenesis in a mouse model of colorectal cancer via suppression of multiple cellular pathways

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