Antimetastatic effect of salvicine on human breast cancer MDA-MB-435 orthotopic xenograft is closely related to Rho-dependent pathway

doi:10.1158/1078-0432.CCR-04-2026

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Antimetastatic effect of salvicine on human breast cancer MDA-MB-435 orthotopic xenograft is closely related to Rho-dependent pathway
	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
	2005-05-01
卷号	11 期号:9 页码:3455-3464
ISSN号	1078-0432
DOI	10.1158/1078-0432.CCR-04-2026
文献子类	Article
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
语种	英语
出版者	AMER ASSOC CANCER RESEARCH
WOS记录号	WOS:000228848000043
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273876]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Ding, J
作者单位	1.Chinese Acad Sci, Grad Sch, Beijing 100864, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Div Phytochem, Shanghai 201203, Peoples R China 4.NCI, Comparat Carcinogenesis Lab, NIEHS, Res Triangle Pk, NC USA
推荐引用方式 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.