ELIZA

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611425 occurrences (No.13 in the rank) during 5 years in the PubMed. [no cache] 500 found

227) In contrast, EP2 agonist (Butaprost) increased cell migration and silymarin effectively reduced butaprost-mediated cell migration.

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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)36 the	(14)5 to	(27)2 RDW	(40)2 likelihood
(2)34 in	(15)4 after	(28)2 awareness	(41)2 maternal
(3)27 risk	(16)4 as	(29)2 bone	(42)2 morbidity
(4)21 null	(17)3 activity	(30)2 but	(43)2 number
(5)20 with	(18)3 among	(31)2 compared	(44)2 over
(6)16 by	(19)3 at	(32)2 concentrations	(45)2 pre-stimulus
(7)15 significantly	(20)3 cell	(33)2 drug	(46)2 production
(8)6 and	(21)3 level	(34)2 during	(47)2 rapidly
(9)6 expression	(22)3 levels	(35)2 fax	(48)2 use
(10)6 from	(23)3 physical	(36)2 functional	(49)2 vascular
(11)5 activation	(24)3 sensitivity	(37)2 hepatic
(12)5 odds	(25)2 MI	(38)2 if
(13)5 serum	(26)2 Math1	(39)2 interest

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--- WordNet output for increased --- =>力の増加 Overview of verb increase The verb increase has 2 senses (first 2 from tagged texts) 1. (86) increase -- (become bigger or greater in amount; "The amount of work increased") 2. (61) increase -- (make bigger or more; "The boss finally increased her salary"; "The university increased the number of students it admitted") Overview of adj increased The adj increased has 1 sense (first 1 from tagged texts) 1. (30) increased -- (made greater in size or amount or degree) --- WordNet end ---