資源描述:
《地塞米松對順鉑誘導人肺腺癌細胞SPC—A1凋亡的抑制作用及分子機制-論文.pdf》由會員上傳分享,免費在線閱讀,更多相關內容在行業(yè)資料-天天文庫。
1、第3l卷第3期生物醫(yī)學工程學雜志V0I.3lNo.32014年6月JournalofBiomedicalEngineeringJune2014地塞米松對順鉑誘導人肺腺癌細胞SPC—A1凋亡的抑制作用及分子機制曹菲張智慧1(成都市西區(qū)醫(yī)院腫瘤科,成都610036)2(四川省腫瘤醫(yī)院腫瘤內科,成都610041)摘要:研究地塞米松(DEX)對順鉑(cDDP)引起的人肺腺癌細胞SPC—A1凋亡的抑制作用及可能的分子機制。將不同濃度的DEX分別加入人肺腺癌細胞SPC—Al體外誘導培養(yǎng)24h后,再用不同濃度CDDP處理
2、SPC—A1細胞48h。MTT法檢測細胞存活率;RT—PCR方法檢測1tmol/IDEX誘導培養(yǎng)不同時間后SPC—A1細胞內血清/糖皮質激素一誘導激酶(SGK一1)和有絲分裂原蛋白激酶(MKP一1)的表達;用生物素標記的抗糖皮質激素受體(GR)抗體對SPC—A1細胞行免疫組化染色來檢測GR的表達。MTT測定結果顯示,SPC—A1細胞經DEX誘導后,對CDDP所致的凋亡有抵抗作用并與DEX濃度呈劑量依賴關系。RT—PCR檢測到DEX誘導培養(yǎng)能提高SGK—l在SPC—A1細胞中的表達,表達量隨時間延長而增加;但
3、未檢測到MKP一1的表達。免疫組化檢測顯示SPC—A1細胞經DEX誘導后GR上調,細胞內GR表達的陽性細胞數明顯高于對照組。結果表明DEX對CDDP引起SPC—A1細胞的凋亡有抑制作用??赡艿姆肿訖C制是通過上調細胞內GR表達,進而上調其通路下游抗凋亡蛋白SGK一1的表達,導致SPC—Al細胞產生抗凋亡作用。關鍵詞:地塞米松;糖皮質激素受體;肺癌;化療;抗凋亡中圖分類號R73—36文獻標志碼ADOI:10.7507/1OO卜55l5.20140122TheInhibitoryEffectsofDexameth
4、asoneonCisplatinInducedApoptosisofHumanLungAdenocarcinomaCellSPC—A1andItsMolecularMechanismCAoFeiZHANGZhihui1(Departmento_,Ontology,ChengduWesternHospital,Chengdu610036,China)2(Department0,MedicalOmology,SichuanProvincialTumorHospital,Chengdu610041,China)A
5、bstract:Theaimofthisstudyistoinvestigatetheapoptoticinhibitionanditsmolecularmechanismofdexametha—sone(DEX)actingoncisplatin(CDDP)一inducedapoptosisofhumanlungadenocarcinomacellSPC—A1.SPC—A1ceilswerepre—culturedinvitrofor24hourswithDEXindifferentconcentrati
6、onsandthenCDDPwasaddedindifferentconcentrationsforculturingforfurther48hours。ThesurvivalratesofthecellsweredeterminedbyMTT.Theex—pressionofserum/glucocorticoid—inducedkinase(SGK一1)andmitogen—activatedproteinkinasephosphatase一1(MKP一1)inSPC—A1ceilsa{terbeing
7、culturedby1~mol/IDEXatdifferenttimewasdetectedbysemi—quantitativeRT~PCRtechnology.Theexpressionofglucocorticoidreceptor(GR)inSPC—A1cellswasmeasuredbyimmunohisto—chemistry(IHC)withbiotin—labeledanti—GR.TheresultsofMTTshowedthatSPC—AlcellshadresistancetoCDDP
8、inducedapoptosiswithpre—culturedDEXandtheresistanceintensitypresentedDEXconcentration-dependent.TheexpressingquantityofSGK一1inSPC—A1cellsstimulatedbyDEXcouldbeelevatedandincreasedwithintentionoftime.buttheexp