ࡱ> ?A> 0zbjbjqq .eez IIIII]]]]q ]$}p#######$%l(#I#II#)))II#)#)):a","%=]F" ##0$" ) )"" )Ia#(v|)dV##@$ ) :   HYPERLINK "javascript:AL_get(this,%20'jour',%20'World%20J%20Gastroenterol.');" World J Gastroenterol. 2007 Oct 28;13(40):5299-305. HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3661&itool=AbstractPlus-def&uid=17879397&db=pubmed&url=http://www.wjgnet.com/1007-9327/13/5299.asp" \t "_blank"  INCLUDEPICTURE "http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.wjgnet.com-images-wjg.gif" \* MERGEFORMATINET   Effects and mechanisms of silibinin on human hepatoma cell lines.  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lah%20JJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Lah JJ,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Cui%20W%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Cui W,  HYPERLINK "http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Hu%20KQ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus" Hu KQ. Division of Gastroenterology, University of California, Irvine Medical Center, 101 The City Drive, Building 53, Suite 113, Orange, CA 92868, United States. AIM: To investigate in vitro effects and mechanisms of silibinin on hepatocellular carcinoma (HCC) cell growth. METHODS: Human HCC cell lines were treated with different doses of silibinin. The effects of silibinin on HCC cell growth and proliferation, apoptosis, cell cycle progression, histone acetylation, and other related signal transductions were systematically examined. RESULTS: We demonstrated that silibinin significantly reduced the growth of HuH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells. Silibinin-reduced HuH7 cell growth was associated with significantly up-regulated p21/CDK4 and p27/CDK4 complexes, down-regulated Rb-phosphorylation and E2F1/DP1 complex. Silibinin promoted apoptosis of HuH7 cells that was associated with down-regulated survivin and up-regulated activated caspase-3 and -9. Silibinin's anti-angiogenic effects were indicated by down-regulated metalloproteinase-2 (MMP2) and CD34. We found that silibinin-reduced growth of HuH7 cells was associated with increased activity of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and decreased p-Akt production, indicating the role of PTEN/PI(3)K/Akt pathway in silibinin-mediated anti-HCC effects. We also demonstrated that silibinin increased acetylation of histone H3 and H4 (AC-H3 and AC-H4), indicating a possible role of altered histone acetylation in silibinin-reduced HCC cell proliferation. CONCLUSION: Our results defined silibinin's in vitro anti-HCC effects and possible mechanisms, and provided a rationale to further test silibinin for HCC chemoprevention. PMID: 17879397 [PubMed - indexed for MEDLINE] RSij< = > ܶɟr]rF5 hS;h6E'CJOJQJ^JaJ-jhS;h6E'0JCJOJQJU^JaJ)hS;h6E'B*CJOJQJ^JaJph2jhS;h6E'B*CJOJQJU^JaJph$hS;h6E'0JCJOJQJ^JaJ-jhS;h6E'0JCJOJQJU^JaJ$hS;h6E'0JCJOJQJ^JaJ$hS;h6E'0JCJOJQJ^JaJ-jhS;h6E'0JCJOJQJU^JaJhS;h6E'OJQJ^J  % KyzH^Hgd6E' Hd ^Hgd6E'H^Hgd6E'^gd6E'8$d%d&d'd-D`@&M NOPQ^gd6E'$$d-DM N3fa$gdS;   % !Kyz׬׬׬ƛƇrehS;h6E'OJQJ^J(hS;h6E'CJOJQJ^JaJmHsH&hS;h6E'5CJOJQJ\^JaJ hS;h6E'CJOJQJ^JaJ2hS;h6E'5>*B*CJOJQJ\^JaJph hS;h6E'CJOJQJ^JaJ)jhS;h6E'CJOJQJU^JaJ&hS;h6E'5CJOJQJ\^JaJ,1h/ =!"#$% Ddto  s A *&--wwwlinkout-icon-def-wjgClick here to readby Ŧ;+xD npy Ŧ;+PNG  IHDRk "vPLTE(,, 6 ;=BJJYZ h!h"g$w&w'w,.-w/w-~f3w4w6w9f:f;fADFDHDA"R"S"GU"LOJ@cl+q1sQRTICCFG<?V o+q+n,p,r,t1~C_VX[HKADt+v+u,w,w1y1{1\]_`XMPQEHg y+z+x,y,|,}1be^SRUQMKMtNżtttnnnkkk^^^WWWWwtRNSebKGDH cmPPJCmp0712HsVIDATHK S@Xm""F hb*EQKYR7da,oߙ_6DZdr$UH2Hlln]LMw;L#mOZ[oا[p8͌;RBM MvVKٙIGBjh?E+,[ëFɘ4w1-_rRJY`hb!+E& H)Ԍ|1,Phb!)H5#crX6n-/L;<~*{Hk4p+u&ԻXrV$BYHT\j$7 Xc%"7$/bQ4j֘gƹ nsdx$Uxr_#;:WOG4- w\a}VWTfuET:4}oCw ?bi%Tt*@ƌQkpфG q,?3Y PWS*K%BkANU>|eu4M'(B5(~B.sJ@n\C+0e^yōg9 ^$PDPfYrEV+~g-P$]DO'ef%HqA;T|n֔)IG6ލl}«,cwy43[ݳQ{#=5_ڶQ[;*59]ʯmب5}82.WlԲM'23s Y TfVSB IENDB` Dd,4   c :ANormalFax01C" Ú <!-- var Menu17879397 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["Compound (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pccompound&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pccompound_mesh&LinkReadableName=Compound%20(MeSH%20Keyword)&IdsFromResult=17879397&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""], ["Substance (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pcsubstance&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pcsubstance_mesh&LinkReadableName=Substance%20(MeSH%20Keyword)&IdsFromResult=17879397&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""], ["Cited in PMC" , "window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=17879397&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus&ordinalpos=1' ", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=17879397&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus' ", "", ""] ] -->JavaScript1.2b!X󆡑NB nX󆡑NBPNG  IHDRfsRGB@}0PLTE{bIDATE!0Eq^uM&VUp\ &C|)"3.8̴(6 jPtsʄ&)NU- \^w& ^eyƾ_c|_^9IENDB`^ 2 0@P`p2( 0@P`p 0@P`p 0@P`p 0@P`p 0@P`p 0@P`p8XV~_HmH nH sH tH @`@ NormalCJ_HaJmH sH tH N"N 6E' Heading 2dd@&[$\$5CJ$\aJ$DA`D Default Paragraph FontRiR  Table Normal4 l4a (k (No List 4U@4 6E' Hyperlink >*ph.X. 6E'Emphasis6]$$ 6E'desc$"$ 6E'noteRO2R 6E' affiliation1xd x^xCJaJPOBP 6E'pmid1xd ^xCJOJQJ^JaJVQV 6E' reviewflag2'56CJ\]aJphq &Oa& 6E'ti2CJaJ:Oq: 6E'featured_linkouts&& 6E'linkbarPK![Content_Types].xmlj0Eжr(΢Iw},-j4 wP-t#bΙ{UTU^hd}㨫)*1P' ^W0)T9<l#$yi};~@(Hu* Dנz/0ǰ $ X3aZ,D0j~3߶b~i>3\`?/[G\!-Rk.sԻ..a濭?PK!֧6 _rels/.relsj0 }Q%v/C/}(h"O = C?hv=Ʌ%[xp{۵_Pѣ<1H0ORBdJE4b$q_6LR7`0̞O,En7Lib/SeеPK!kytheme/theme/themeManager.xml M @}w7c(EbˮCAǠҟ7՛K Y, e.|,H,lxɴIsQ}#Ր ֵ+!,^$j=GW)E+& 8PK!Ptheme/theme/theme1.xmlYOo6w toc'vuر-MniP@I}úama[إ4:lЯGRX^6؊>$ !)O^rC$y@/yH*񄴽)޵߻UDb`}"qۋJחX^)I`nEp)liV[]1M<OP6r=zgbIguSebORD۫qu gZo~ٺlAplxpT0+[}`jzAV2Fi@qv֬5\|ʜ̭NleXdsjcs7f W+Ն7`g ȘJj|h(KD- dXiJ؇(x$( :;˹! I_TS 1?E??ZBΪmU/?~xY'y5g&΋/ɋ>GMGeD3Vq%'#q$8K)fw9:ĵ x}rxwr:\TZaG*y8IjbRc|XŻǿI u3KGnD1NIBs RuK>V.EL+M2#'fi ~V vl{u8zH *:(W☕ ~JTe\O*tHGHY}KNP*ݾ˦TѼ9/#A7qZ$*c?qUnwN%Oi4 =3ڗP 1Pm \\9Mؓ2aD];Yt\[x]}Wr|]g- eW )6-rCSj id DЇAΜIqbJ#x꺃 6k#ASh&ʌt(Q%p%m&]caSl=X\P1Mh9MVdDAaVB[݈fJíP|8 քAV^f Hn- "d>znNJ ة>b&2vKyϼD:,AGm\nziÙ.uχYC6OMf3or$5NHT[XF64T,ќM0E)`#5XY`פ;%1U٥m;R>QD DcpU'&LE/pm%]8firS4d 7y\`JnίI R3U~7+׸#m qBiDi*L69mY&iHE=(K&N!V.KeLDĕ{D vEꦚdeNƟe(MN9ߜR6&3(a/DUz<{ˊYȳV)9Z[4^n5!J?Q3eBoCM m<.vpIYfZY_p[=al-Y}Nc͙ŋ4vfavl'SA8|*u{-ߟ0%M07%<ҍPK! ѐ'theme/theme/_rels/themeManager.xml.relsM 0wooӺ&݈Э5 6?$Q ,.aic21h:qm@RN;d`o7gK(M&$R(.1r'JЊT8V"AȻHu}|$b{P8g/]QAsم(#L[PK-![Content_Types].xmlPK-!֧6 +_rels/.relsPK-!kytheme/theme/themeManager.xmlPK-!Ptheme/theme/theme1.xmlPK-! ѐ' theme/theme/_rels/themeManager.xml.relsPK] z  z z Ri<=z XXCXXX8@0(  B S  ? 鴀!관"봀!촀\"\ﴀܐ\ܑ |     ##|    9*urn:schemas-microsoft-com:office:smarttagsplace= *urn:schemas-microsoft-com:office:smarttags PlaceName= *urn:schemas-microsoft-com:office:smarttags PlaceTypeB*urn:schemas-microsoft-com:office:smarttagscountry-region9*urn:schemas-microsoft-com:office:smarttagsState8*urn:schemas-microsoft-com:office:smarttagsCity;*urn:schemas-microsoft-com:office:smarttagsaddress>*urn:schemas-microsoft-com:office:smarttags PostalCode:*urn:schemas-microsoft-com:office:smarttagsStreet `  [h\eiwELMX#,!)Wbhr + 0 6 p s     _ f g r v  ( 1 K x | SivylrK x | 3333k| y y | ctq{5V^`CJOJQJo(^`CJOJQJo(opp^p`CJOJQJo(@ @ ^@ `CJOJQJo(^`CJOJQJo(^`CJOJQJo(^`CJOJQJo(^`CJOJQJo(PP^P`CJOJQJo(^`CJOJQJo(^`CJOJQJo(opp^p`CJOJQJo(@ @ ^@ `CJOJQJo(^`CJOJQJo(^`CJOJQJo(^`CJOJQJo(^`CJOJQJo(PP^P`CJOJQJo(ctq{5 ^6La:$7O xx`hFAtHcDFttxxL$7O$7O`hFAtKR$7Oh2WDMh\tKRtHch2WHFttS;6E'L:\6z | @SXSSz @@UnknownG"Times New Roman5Symbol3. "Arial7.@ Calibri?5 "Courier New;WingdingsA$BCambria Math"qhZFb#g   !24u u  3QHP ?6E'2!xx/(17) Reduced Incidence of Neoplasia (Silymarin)Mina mfayez  Oh+'0 (4 T ` lx0(17) Reduced Incidence of Neoplasia (Silymarin)Mina  Normal.dotmmfayez2Microsoft Office Word@e@R@ o= ՜.+,D՜.+,d  hp   Minapharmu  0(17) Reduced Incidence of Neoplasia (Silymarin) Title 8@ _PID_HLINKSA<"http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Hu%20KQ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus Qn http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Cui%20W%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus Ut http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lah%20JJ%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus 6-http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3661&itool=AbstractPlus-def&uid=17879397&db=pubmed&url=http://www.wjgnet.com/1007-9327/13/5299.asp 2P;javascript:AL_get(this, 'jour', 'World J Gastroenterol.');   !"#$%&'()*+,-/012345789:;<=@Root Entry F}=BData C1Table)WordDocument.SummaryInformation(.DocumentSummaryInformation86CompObjy  F'Microsoft Office Word 97-2003 Document MSWordDocWord.Document.89q