Abstract:
:Signal transducers and activators of transcription 3 (STAT3) signaling is persistently activated in many types of cancer cells, and represents a valid target for anticancer drug design. However, few reports have described the constitutive activation of STAT3 in human sarcoma cells. In this study, we demonstrate that the STAT3 signaling pathway is constitutively activated in human rhabodomyosarcoma cells (RH28, RH30, and RD2). We also investigated the inhibitory effects of two newly developed small molecules, LLL12 and FLLL32, on the STAT3 signaling pathway in human rhabodomyosarcoma cells. Both LLL12 and FLLL32 downregulated STAT3 constitutively and interleukin-6 (IL-6) stimulated phosphorylated STAT3 (p-STAT3). The inhibition of STAT3 via LLL12 and FLLL32 was confirmed by the inhibition of STAT3 DNA binding activity. The downstream targets of STAT3, cyclin D1, Bcl-xL, and survivin were also downregulated by LLL12 and FLLL 32 at both messenger RNA and protein levels. The potency of LLL12 and FLLL32 to inhibit proliferation/viability in human rhabodomyosarcoma cells (RH28, RH30, and RD2) was higher than that of the 5 previously reported Janus kinase 2 (JAK2)/STAT3 inhibitors (LLL3, WP1066, Stattic, S3I-201, and AG490) and curcumin. Thus, in this study, we investigated the inhibitory effects of two STAT3 inhibitors, LLL12 and FLLL32, on the STAT3 signaling pathway in human rhabodomyosarcoma cells; we also demonstrated their higher potency in inhibiting proliferation on human rhabodomyosarcoma cells as compared to other five JAK2/STAT3 inhibitors and curcumin.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Wei CC,Ball S,Lin L,Liu A,Fuchs JR,Li PK,Li C,Lin Jsubject
Has Abstractpub_date
2011-01-01 00:00:00pages
279-85issue
1eissn
1019-6439issn
1791-2423journal_volume
38pub_type
杂志文章abstract::The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin and tryptase. The purpose of this study was to clarify the role of PAR-2 in proliferation of human pancreatic cancer cells. PAR-2 mRNA and protein expression were detected by RT-PCR and Western blotting i...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-06-01 00:00:00
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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更新日期:2007-02-01 00:00:00
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abstract::Galiximab is a primatized monoclonal antibody that targets CD80 expressed on malignant B cells and is being studied in the clinic as a potential treatment for follicular NHL. We have recently reported that galiximab signals B-NHL cells in vitro and inhibits cell growth and sensitizes resistant tumor cells to apoptosis...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.1986
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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doi:
更新日期:2008-03-01 00:00:00
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journal_title:International journal of oncology
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doi:
更新日期:1994-09-01 00:00:00
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doi:10.3892/ijo.2013.2047
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journal_title:International journal of oncology
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