槲皮素抑制乳腺癌细胞迁移侵袭及分子机制研究(1)
[摘要]目的：探究槲皮素(naringenin)对乳腺癌细胞MDA-MB-231转移的影响及其作用机制。方法：MTT法观察经不同浓度槲皮素对乳腺癌细胞MDA-MB-231生长能力的影响;划痕实验(woundhealing)及Transwell实验分析考查槲皮素对MDA-MB-231水平运动能力的影响;采用Westernblotting考察槲皮素对MDA-MB-231细胞整合素Integrinβ3，β1及基质金属蛋白酶MMP-2(matrixmetalloproteinases-2，MMP-2)，MMP-9蛋白表达的影响;运用计算机虚拟对接技术体外评价槲皮素与整合素Integrinβ3的结合能力。结果：槲皮素可以剂量依赖性抑制MDA-MB-231细胞的增殖;Woundhealing实验和Transwell小室迁移实验中，随着槲皮素浓度提高，MDA-MB-231迁移数目呈递减趋势;随着槲皮素浓度的提高，乳腺癌细胞侵袭能力呈递减趋势;槲皮素可以剂量依赖性抑制Integrinβ3蛋白表达，而对Integrinβ1的表达不甚明显，此外槲皮素可以显著抑制MMP-2和MMP-9的蛋白表达;计算机虚拟对接结果发现槲皮素与Integrinβ3的结合能力数值为较低负值，表明槲皮素与Integrinβ3有较好的亲和力。结论：槲皮素具有抑制MDA-MB-231乳腺癌细胞生长能力，阻断MDA-MB-231细胞迁移、运动以及侵袭，其机制为槲皮素与Integrinβ3结合后，下调MMP-2，MMP-9的表达。
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[关键词]槲皮素;计算机虚拟对接;MDA-MB-231;迁移侵袭;MMPs;Integrin
Studyoneffectofnaringeninininhibitingmigrationandinvasionof
breastcancercellsanditsmolecularmechanism
SUNYi，GUJun*
(DepartmentofPharmacy，theFirstAffiliatedHospitalofSuzhouUniversity，Suzhou215006，China)
[Abstract]Objective：TostudytheeffectofnadroparininthemigrationofbreastcancercellsMDA-MB-231anditsactionmechanism.Method：TheMTTtestwasadoptedtoobservetheeffectofdifferentconcentrationsofnaringeninonthegrowthcapacityofbreastcancercellsMDA-MB-231.WoundhealingandtranswellexperimentanalysiswereconductedtodetecttheeffectofnaringeninonthemigrationofbreastcancercellsMDA-MB-231.WesternblottingwasadoptedtoinvestigatetheeffectofnaringeninonproteinexpressionsofMDA-MB-231cellIntegrinβ3，β1andmatrixmetalloproteinaseMMP-2andMMP-9.ThecomputervirtualdockingtechniquewasusedtoevaluatethecombiningcapacityofnaringeninandIntegrinβ3invitro.Result：NaringenininhibitedthemigrationofMDA-MB-231cellsinadose-dependentmanner.Inwoundhealingandtranswellexperiments，withtheincreaseintheconcentrationofnaringenin，thenumberofmigrantMDA-MB-231cellsandtheinvasioncapacityofbreastcancercellsdecreased.NaringenincouldinhibittheproteinexpressionofIntegrinβ3inadose-dependentmanner，butwithunobviouseffectonexpressionofIntegrinβ1.Besides，naringenincouldsignificantlyinhibittheproteinexpressionsofMMP-2andMMP-9.TheresultsofthecomputervirtualdockingshowedanegativevalueinthecombiningcapacitybetweennaringeninandIntegrinβ3，indicatingthehighaffinitybetweenthem.Conclusion：NaringenincaninhibitthegrowthcapacityofbreastcancercellsMDA-MB-231andblockthemigrationandinvasionofbreastcancercellsMDA-MB-231.Itsmechanismistodown-regulateMMP-2andMMP-9expressionsaftercombiningwithIntegrinβ3.
[Keywords]naringenin;computervirtualdocking;MDA-MB-231;migrationandinvasion;MMPs;Integrin
doi：10.4268/cjcmm20150630, 百拇医药(孙怡 顾君)
, http://www.100md.com
[关键词]槲皮素;计算机虚拟对接;MDA-MB-231;迁移侵袭;MMPs;Integrin
Studyoneffectofnaringeninininhibitingmigrationandinvasionof
breastcancercellsanditsmolecularmechanism
SUNYi，GUJun*
(DepartmentofPharmacy，theFirstAffiliatedHospitalofSuzhouUniversity，Suzhou215006，China)
[Abstract]Objective：TostudytheeffectofnadroparininthemigrationofbreastcancercellsMDA-MB-231anditsactionmechanism.Method：TheMTTtestwasadoptedtoobservetheeffectofdifferentconcentrationsofnaringeninonthegrowthcapacityofbreastcancercellsMDA-MB-231.WoundhealingandtranswellexperimentanalysiswereconductedtodetecttheeffectofnaringeninonthemigrationofbreastcancercellsMDA-MB-231.WesternblottingwasadoptedtoinvestigatetheeffectofnaringeninonproteinexpressionsofMDA-MB-231cellIntegrinβ3，β1andmatrixmetalloproteinaseMMP-2andMMP-9.ThecomputervirtualdockingtechniquewasusedtoevaluatethecombiningcapacityofnaringeninandIntegrinβ3invitro.Result：NaringenininhibitedthemigrationofMDA-MB-231cellsinadose-dependentmanner.Inwoundhealingandtranswellexperiments，withtheincreaseintheconcentrationofnaringenin，thenumberofmigrantMDA-MB-231cellsandtheinvasioncapacityofbreastcancercellsdecreased.NaringenincouldinhibittheproteinexpressionofIntegrinβ3inadose-dependentmanner，butwithunobviouseffectonexpressionofIntegrinβ1.Besides，naringenincouldsignificantlyinhibittheproteinexpressionsofMMP-2andMMP-9.TheresultsofthecomputervirtualdockingshowedanegativevalueinthecombiningcapacitybetweennaringeninandIntegrinβ3，indicatingthehighaffinitybetweenthem.Conclusion：NaringenincaninhibitthegrowthcapacityofbreastcancercellsMDA-MB-231andblockthemigrationandinvasionofbreastcancercellsMDA-MB-231.Itsmechanismistodown-regulateMMP-2andMMP-9expressionsaftercombiningwithIntegrinβ3.
[Keywords]naringenin;computervirtualdocking;MDA-MB-231;migrationandinvasion;MMPs;Integrin
doi：10.4268/cjcmm20150630, 百拇医药(孙怡 顾君)