Document Detail


Growth suppression of cervical carcinoma by pigment epithelium-derived factor via anti-angiogenesis.
MedLine Citation:
PMID:  20364117     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pigment epithelium-derived factor (PEDF), an angiogenesis inhibitor with multiple other functions, balances angiogenesis in the eye and blocks tumor progression. Cervical cancer, an angiogenesis-dependent tumor, is the second most common cancer in women without effective treatment. It has been reported that PEDF can inhibit several types of tumors, however, the potential of PEDF for the treatment of cervical carcinoma has not been well explored. The present study was designed to investigate the effect of recombinant PEDF on the neovascularization and growth of cervical carcinoma. We found for the first time that PEDF was downregulated apparently in human cervical carcinoma nests compared to either normal cervical epithelium or nonneoplastic peritumoral epithelium, suggesting potential anti-angiogenesis function by supplement of PEDF in cervical carcinoma. Intraperitoneal injection of PEDF in xenografted cervical carcinoma mice suppressed tumor growth with 68% reduction. Microvessel density in tumor tissues treated with PEDF was significantly decreased. PEDF dose-dependently inhibited proliferation and induced apoptosis of endothelial cells, but had no direct effect on proliferation and apoptosis of Hela cells under both normoxia and hypoxia. These results suggested that PEDF suppressed tumor growth by blocking angiogenesis instead of a direct cytotoxic effect on tumor cells. VEGF, a major angiogenic stimulator, was downregulated by PEDF in Hela cells by downregulation of HIF-1α, a crucial transcriptional factor for VEGF expression. Downregulation of VEGF expression in tumor cells through inhibiting HIF-1α, thus attenuating the paracrine effect of VEGF on endothelial cells, may represent a mechanism for the anti-angiogenic activity of PEDF.
Authors:
Jun Yang; Shuqin Chen; Xuan Huang; Jiande Han; Qingsong Wang; Dingbo Shi; Rui Cheng; Guoquan Gao; Xia Yang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-08
Journal Detail:
Title:  Cancer biology & therapy     Volume:  9     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-09-21     Completed Date:  2011-02-18     Revised Date:  2011-03-30    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  967-74     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Zhongshan Medical School of Sun Yat-sen University, Guangzhou, Guangdong Province, China.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / pharmacology,  therapeutic use*
Animals
Apoptosis / drug effects
Cell Hypoxia / drug effects
Down-Regulation
Endothelial Cells / drug effects
Eye Proteins / pharmacology,  therapeutic use*
Female
Hela Cells
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Mice
Neovascularization, Pathologic / drug therapy
Nerve Growth Factors / pharmacology,  therapeutic use*
Recombinant Proteins / therapeutic use
Serpins / pharmacology,  therapeutic use*
Tumor Burden / drug effects
Uterine Cervical Neoplasms / blood supply,  drug therapy*,  metabolism,  pathology
Vascular Endothelial Growth Factor A / metabolism
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Eye Proteins; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Nerve Growth Factors; 0/Recombinant Proteins; 0/Serpins; 0/Vascular Endothelial Growth Factor A; 0/pigment epithelium-derived factor
Comments/Corrections
Comment In:
Cancer Biol Ther. 2010 Jun;9(12):975-7   [PMID:  20424516 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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