舒林酸對卵巢癌血管生成的影響及機制探討.pdf

1、復旦大學博士學位論文舒林酸對卵巢癌血管生成的影響及機制探討姓名：劉素英申請學位級別：博士專業(yè)：婦科腫瘤指導教師：豐有吉2002.4.1TheExperimentalStudyofSulindacoHtheAngiogenesisofOvarianEpithelialCancerAbstractObjectivesToinvestigatetheeffectsofsulindacmetabolitesontheproliferation，

2、apoptosisandmigrationinducedbySKOV3inhumanumbilicalveinendothelialcelllineECV304invitro；ToinvestigatetheeffectsofsulindaconascitesformationandtumorgrowthinnudemiceinducedbySKOV3celllineMethodsTheproliferationofECV304wasd

3、eterminedbymethylthiazolyltetrazolium(MTT)methodThecellcycle，apoptosisandtheultrastructureofECV304weredetectedbyflowcytometry(FCM)andelectronmicroscopyrespectively；Thecellmigrationwasdeterminedbyusingtranswell—boydomsyst

4、em；TheexpressionofVEGF，bFGFMMP2andMMP9oftumorcellsweredeterminedbyimmunohistochemical，RT—PCRandzamographymethods，theapoptosisoftumorcellsweredeterminedbyusingTUNELandelectronmicroscopymethodsResultsMTTshowedthatsulfidein

5、hibitedtheproliferationofECV304FCMshowedthatsulfidechangedcellcycledistributionComparedwiththecontrolgroup，sulfidecouldreducetheproportionofGIphase，increasetheproportionofSphaseandG2Mphasesignificantly(P001)Alsoit’Ssulfi

6、deinducescellapoptosissignificantly(P001)；sulfonehasnoeffectoncellproliferation，cellcycleandcellmorphorlogyThemigrationofvascularendothelialceilsinducedbySKOV3wasinhibitedbysulindacsulfidesignificantly(P001)Themalignanta

7、scitesformationandintraperitonealtumorburdendecreasedsignificantlyaftertreatingwithsulindac(P001)Tumorvolumetransplantedinthesubcutaneousdecreasedaftertreatingwithsulindacandtaxol(P005，)；TheexpressionofVEGFandMMP2weredow

8、nregulatedbysutindacandtaxol(PO05)Themicrovasculardensitydecreasedsignificantly(P0O1)Conclusions1SulindacsulfidecouldreducetheviabilityofECV304，changethecellcycledistribution，arrestthecellcycleinG2Mphaseandinduceitsapopt