ELIZA

return kwic search for through out of >500 occurrences
437431 occurrences (No.38 in the rank) during 5 years in the PubMed. [cache]

255) 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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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)113 the	(12)3 biological	(23)2 direct	(34)2 low
(2)51 a	(13)3 both	(24)2 evidence	(35)2 maternal
(3)11 an	(14)3 cortical	(25)2 focus	(36)2 paracrine
(4)10 which	(15)3 histological	(26)2 four	(37)2 promoting
(5)5 their	(16)3 infancy	(27)2 human	(38)2 rat
(6)4 activation	(17)3 interaction	(28)2 information,	(39)2 reward
(7)4 its	(18)3 simulation	(29)2 inhibition	(40)2 skin
(8)4 median	(19)2 2012	(30)2 interactions	(41)2 such
(9)4 three	(20)2 August	(31)2 international	(42)2 these
(10)4 use	(21)2 PCR-based	(32)2 intersection
(11)3 analysis	(22)2 different	(33)2 interviews

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--- WordNet output for through --- =>直通の, のために, の間じゅう, 終わって, を貫いて, の中を通って, のいたるところに, を通じて Overview of adj through The adj through has 2 senses (first 1 from tagged texts) 1. (4) done, through, through with -- (having finished or arrived at completion; "certain to make history before he's done"; "it's a done deed"; "after the treatment, the patient is through except for follow-up"; "almost through with his studies") 2. through -- ((of a route or journey etc.) continuing without requiring stops or changes; "a through street"; "a through bus"; "through traffic") Overview of adv through The adv through has 5 senses (first 3 from tagged texts) 1. (5) through -- (from beginning to end; "read this book through") 2. (2) through -- (over the whole distance; "this bus goes through to New York") 3. (1) through -- (to completion; "think this through very carefully!") 4. through -- (in diameter; "this cylinder measures 15 inches through") 5. through, through and through -- (throughout the entire extent; "got soaked through in the rain"; "I'm frozen through"; "a letter shot through with the writer's personality"; "knew him through and through"; "boards rotten through and through") --- WordNet end ---