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Inhibition of angiogenic activity of hypoxic fibroblast cell line MRC-5 in vitro by topotecan.
MedLine Citation:
PMID:  21061095     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Tumor stroma plays an important role in cancer development. Stromal fibroblasts often represent the majority of stromal cells within various types of human carcinomas, and they are competent to promote the growth of cancer cells and to enhance tumor angiogenesis. However, the effect of known anti-cancer drugs on stromal cells has not been thoroughly investigated. Topotecan (TPT) is a semi-synthetic analogue of camptothecin, and several studies have shown that TPT inhibited angiogenesis via its direct effect on vascular endothelial cells. Here, we studied the effect of TPT on pro-angiogenesis action of hypoxic fibroblasts (MRC-5 cells). Growth inhibition was analyzed by MTT assay, while transwell assay and tube formation assay were used to evaluate the inhibition by TPT of hypoxic MRC-5 cell angiogenic activity in vitro. ELISA and Western blot analysis were used to investigate the related mechanism. Pretreatment of MRC-5 with TPT remarkably attenuated the induction of migration and tube formation of HUVECs by conditioned medium from hypoxic MRC-5 cells. In addition, topotecan decreased hypoxia-induced VEGF production by MRC-5 cells. Moreover, topotecan inhibits HIF-1α and α-SMA protein expression in hypoxic MRC-5 cells. Our data suggest that TPT inhibits hypoxic fibroblast angiogenic activity via downregulation of HIF-1α and prevention of fibroblast differentiation to myofibroblast.
Authors:
Liqiang Zhou; Li Sun; Sensen Lin; Dongdong Fang; Renping Zhao; Jing Zhu; Jin Liu; Liang Chen; Wenting Shi; Shengtao Yuan; Danni Zhu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-11-9
Journal Detail:
Title:  Medical oncology (Northwood, London, England)     Volume:  -     ISSN:  1559-131X     ISO Abbreviation:  -     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9435512     Medline TA:  Med Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Jiangsu Center for Drug Screening, China Pharmaceutical University, 210009, Nanjing, People's Republic of China.
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