中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Antimetastatic effect of salvicine on human breast cancer mda-mb-435 orthotopic xenograft is closely related to rho-dependent pathway

文献类型:期刊论文

作者Lang, JY; Chen, H; Zhou, J; Zhang, YX; Zhang, XW; Li, MH; Lin, LP; Zhang, JS; Waalkes, MP; Ding, J
刊名Clinical cancer research
出版日期2005-05-01
卷号11期号:9页码:3455-3464
ISSN号1078-0432
通讯作者Ding, j()
英文摘要Purpose: salvicine is a novel dna topoisomerase ii inhibitor with potent anticancer activity. in present study, the effect of salvicine against metastasis is evaluated using human breast carcinoma orthotopic metastasis model and its mechanism is further investigated both in animal and cellular levels. experimental design: the mda-mb-435 orthotopic xenograft model was applied to detect the antimetastatic effect of salvicine. potential target candidates were detected and analyzed by microarray technology. candidates were verified and explored by reverse transcription-pcr and western blot. salvicine activities on stress fiber formation, invasion, and membrane translocation were further investigated by immunofluorescence, invasion, and ultracentrifugal assays. results: salvicine significantly reduced the lung metastatic foci of mda-mb-435 orthotopic xenograft, without affecting primary tumor growth obviously. a comparison of gene expression profiles of primary tumors and lung metastatic focus between salvicine-treated and untreated groups using the clotech atlas human cancer 1.2 cdna microarray revealed that genes involved in tumor metastasis, particularly those closely related to cell adhesion and motility, were obviously down-regulated, including fibronectin, integrin a3, integrin beta 3, integrin beta 5, fak, paxillin, and rhoc. furthermore, salvicine significantly down-regulated rhoc at both mrna and protein levels, greatly inhibited stress fiber formation and invasiveness of mda-mb-435 cells, and markedly blocked translocation of both rhoa and rhoc from cytosol to membrane. conclusion: the unique antimetastatic action of salvicine, particularly its specific modulation of cell motility in vivo and in vitro, is closely related to rho-dependent signaling pathway.
WOS关键词TUMOR-CELL INVASION ; ACTIN STRESS FIBERS ; BINDING PROTEIN RHO ; SMALL GTPASES ; LYSOPHOSPHATIDIC-ACID ; ALPHA-6-BETA-4 INTEGRIN ; LAMELLAE FORMATION ; FOCAL ADHESIONS ; FAMILY GTPASES ; METASTASIS
WOS研究方向Oncology
WOS类目Oncology
语种英语
WOS记录号WOS:000228848000043
出版者AMER ASSOC CANCER RESEARCH
URI标识http://www.irgrid.ac.cn/handle/1471x/2377484
专题中国科学院大学
通讯作者Ding, J
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Phytochem, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Grad Sch, Beijing 100864, Peoples R China
4.NCI, Comparat Carcinogenesis Lab, NIEHS, Res Triangle Pk, NC USA
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GB/T 7714
Lang, JY,Chen, H,Zhou, J,et al. Antimetastatic effect of salvicine on human breast cancer mda-mb-435 orthotopic xenograft is closely related to rho-dependent pathway[J]. Clinical cancer research,2005,11(9):3455-3464.
APA Lang, JY.,Chen, H.,Zhou, J.,Zhang, YX.,Zhang, XW.,...&Ding, J.(2005).Antimetastatic effect of salvicine on human breast cancer mda-mb-435 orthotopic xenograft is closely related to rho-dependent pathway.Clinical cancer research,11(9),3455-3464.
MLA Lang, JY,et al."Antimetastatic effect of salvicine on human breast cancer mda-mb-435 orthotopic xenograft is closely related to rho-dependent pathway".Clinical cancer research 11.9(2005):3455-3464.

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来源:中国科学院大学

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