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731925 occurrences (No.6 in the rank) during 5 years in the PubMed. [no cache] 500 found

389) Moreover, PGE2 increased EP2 expression through activation of positive feedback mechanism, and PGE2 -induced EP2 expression, as well as basal EP2 levels, were reduced in silymarin-treated cells.

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PMID:24127286 DOI:10.1002/mc.22092

2015 Molecular carcinogenesis

* Silymarin suppresses the PGE2 -induced cell migration through inhibition of EP2 activation; G protein-dependent PKA-CREB and G protein-independent Src-STAT3 signal pathways.

- Silymarin has been known as a chemopreventive agent, and possesses multiple anti-cancer activities including induction of apoptosis, inhibition of proliferation and growth, and blockade of migration and invasion. However, whether silymarin could inhibit prostaglandin (PG) E2 -induced renal cell carcinoma (RCC) migration and what are the underlying mechanisms are not well elucidated. Here, we found that silymarin markedly inhibited PGE2 -stimulated migration. PGE2 induced G protein-dependent CREB phosphorylation via protein kinase A (PKA) signaling, and PKA inhibitor (H89) inhibited PGE2 -mediated migration. Silymarin reduced PGE2 -induced CREB phosphorylation and CRE-promoter activity. PGE2 also activated G protien-independent signaling pathways (Src and STAT3) and silymarin reduced PGE2 -induced phosphorylation of Src and STAT3. Inhibitor of Src (Saracatinib) markedly reduced PGE2 -mediated migration. We found that EP2, a PGE2 receptor, is involved in PGE2 -mediated cell migration. Down regulation of EP2 by EP2 siRNA and EP2 antagonist (AH6809) reduced PGE2 -inudced migration. In contrast, EP2 agonist (Butaprost) increased cell migration and silymarin effectively reduced butaprost-mediated cell migration. Moreover, PGE2 increased EP2 expression through activation of positive feedback mechanism, and PGE2 -induced EP2 expression, as well as basal EP2 levels, were reduced in silymarin-treated cells. Taken together, our study demonstrates that silymarin inhibited PGE2 -induced cell migration through inhibition of EP2 signaling pathways (G protein dependent PKA-CREB and G protein-independent Src-STAT3).

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(1)183 of	(11)7 is	(21)3 indicating	(31)2 level,
(2)50 in	(12)6 analysis	(22)3 on	(32)2 pattern
(3)28 levels	(13)4 at	(23)3 via	(33)2 profiling
(4)25 and	(14)4 profile	(24)2 alkaline	(34)2 regulation
(5)23 was	(15)4 through	(25)2 between	(35)2 that
(6)21 null	(16)4 were	(26)2 but	(36)2 whereas
(7)11 level	(17)3 are	(27)2 cell	(37)2 which
(8)10 patterns	(18)3 changes	(28)2 during	(38)2 with
(9)8 profiles	(19)3 data	(29)2 from
(10)7 by	(20)3 for	(30)2 increased

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--- WordNet output for expression --- =>表現すること, 式, 表現, 表示, 言い回し, 表現法, 表情 Overview of noun expression The noun expression has 9 senses (first 6 from tagged texts) 1. (23) expression, look, aspect, facial expression, face -- (the feelings expressed on a person's face; "a sad expression"; "a look of triumph"; "an angry face") 2. (18) expression, manifestation, reflection, reflexion -- (expression without words; "tears are an expression of grief"; "the pulse is a reflection of the heart's condition") 3. (15) expression, verbal expression, verbalism -- (the communication (in speech or writing) of your beliefs or opinions; "expressions of good will"; "he helped me find verbal expression for my ideas"; "the idea was immediate but the verbalism took hours") 4. (5) saying, expression, locution -- (a word or phrase that particular people use in particular situations; "pardon the expression") 5. (4) formulation, expression -- (the style of expressing yourself; "he suggested a better formulation"; "his manner of expression showed how much he cared") 6. (4) formula, expression -- (a group of symbols that make a mathematical statement) 7. expression -- ((genetics) the process of expressing a gene) 8. construction, grammatical construction, expression -- (a group of words that form a constituent of a sentence and are considered as a single unit; "I concluded from his awkward constructions that he was a foreigner") 9. expression -- (the act of forcing something out by squeezing or pressing; "the expression of milk from her breast") --- WordNet end ---