Abstract:
AIM:The purpose of this study was to reveal the effects of hepatocyte growth factor (HGF) variants on human breast cancer cells and the differential signaling pathways of the variants in controlling cell proliferation and invasion. METHODS:Four HGF variants (NK1, NK2, NK3, and NK4) were created by gene engineering, and the variant DNA fragments were cloned into pGEM-T for DNA sequencing and then transferred to a pTrcHis-A plasmid for expression. Recombinant proteins were purified from Escherichia coli, and a series of assays, including cell proliferation and invasion were carried out. Phosphorylated components in the HGF-c-Met and STAT (signal transducers and activators of transcription) pathways were detected by immunoprecipitation-Western blots. RESULTS:All the HGF variants inhibited the vigorous growth of the cancer cells differently and dose-dependently, but the effect of NK3 or NK4 was 7.5-fold higher than NK1 or NK2. In addition, the assays for the phosphorylation of the components in the HGF-c-Met pathway showed that NK3 and NK4 inhibited invasion via the STAT pathway, whereas NK1 and NK2 were via the HGF-c-Met pathway. CONCLUSION:The engineered HGF variants inhibited the proliferation of human breast cancer cells via different signaling pathways, NK1 and NK2 via the HGF-c-Met pathways, and NK3 and NK4 via the STAT pathway, the latter being a possible key route for the inhibition of cell invasion. All of the HGF variants have the potential to become pharmaceutical drugs in the treatment of human cancer.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Yin YL,Chen HL,Kuo HM,He SPdoi
10.1111/j.1745-7254.2008.00799.xsubject
Has Abstractpub_date
2008-06-01 00:00:00pages
728-35issue
6eissn
1671-4083issn
1745-7254journal_volume
29pub_type
杂志文章abstract:AIM:To investigate the role of CYP2E1 in isoniazid (INH)-induced hepatotoxicity and the influence of rifampicin (RFP) on INH-induced liver injury. METHODS:Rats were treated with INH alone (100 mg/kg, ip) or co-administered with RFP (100 mg/kg, ig) for 10 d and 21 d. Hepatotoxicity was assayed by plasma enzymes (sALT, ...
journal_title:Acta pharmacologica Sinica
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journal_title:Acta pharmacologica Sinica
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abstract:AIM:To investigate effects of CpG oligodeoxynucleotide (CpG ODN) on the mRNA expression of transcription factors GATA binding protein 3 (GATA-3) and T-box expressed in T cells (T-bet) in asthmatic mice. METHODS:An asthmatic mouse model was established and treated with CpG ODN. Total inflammatory cells and eosinophils ...
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pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00861.x
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pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00462.x
更新日期:2006-12-01 00:00:00
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abstract:AIM:To investigate the ability of an antisense RNA eukaryotic expression plasmid pcDNA3.1/survivin in down-regulating the expression level of survivin mRNA and survivin protein and reversed multidrug resistance (MDR) in adriamycin-resistant HL-60/ADR cell line. METHODS:The expression of survivin mRNA was measured by R...
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更新日期:2003-12-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00525.x
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更新日期:2002-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/aps.2009.68
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更新日期:2008-09-01 00:00:00
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