Abstract：
:Signal transducer and activator of transcription 3 (STAT3) is expressed aberrantly in multiple tumors, including gastric cancer (GC). STAT3 overexpression and excessive activation have been confirmed to play vital roles in tumorigenesis. Cucurbitacin B (CuB) is a natural product with potent anti-cancer activities in solid tumors. Here, we systematically studied the underlying molecular mechanisms of CuB inhibition of GC both in vitro and in vivo. In GC cell lines, nanomolar concentrations of CuB decreased the phosphorylation of TYR-705 in STAT3 and suppressed STAT3 target gene expression, including c-Myc and Bcl-xL. Computational docking analysis showed that CuB interacts with the DNA-binding domain of STAT3 at several hydrophobic residues. In addition, pull-down experiments showed that CuB is a direct inhibitor of STAT3. CuB in combination with the conventional chemotherapy drug cisplatin exerted enhanced cytotoxicity in GC cells, possibly due to the potentiated inhibition of STAT3 activation. Moreover, a xenograft mouse model confirmed the therapeutic effect of CuB in vivo. These characteristics render CuB a promising candidate drug for further development in the design of new effective STAT3 inhibitors for treating GC.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Xu J,Chen Y,Yang R,Zhou T,Ke W,Si Y,Yang S,Zhang T,Liu X,Zhang L,Xiang K,Guo Y,Liu Ydoi
10.1016/j.abb.2020.108314subject
Has Abstractpub_date
2020-05-15 00:00:00pages
108314eissn
0003-9861issn
1096-0384pii
S0003-9861(19)31055-0journal_volume
684pub_type
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doi：10.1016/0003-9861(91)90448-r
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更新日期：1984-08-15 00:00:00
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更新日期：2005-09-01 00:00:00
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更新日期：1983-03-01 00:00:00
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doi：10.1016/0003-9861(83)90371-5
更新日期：1983-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1006/abbi.1995.1257
更新日期：1995-04-20 00:00:00
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pub_type： 杂志文章
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更新日期：1992-12-01 00:00:00
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pub_type： 杂志文章
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更新日期：2009-05-15 00:00:00
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更新日期：2014-12-15 00:00:00
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更新日期：2003-12-01 00:00:00
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更新日期：2021-01-07 00:00:00
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journal_title：Archives of biochemistry and biophysics
pub_type： 杂志文章,评审
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更新日期：2010-09-15 00:00:00
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pub_type： 杂志文章
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更新日期：2000-07-15 00:00:00
