吗啡对顺铂诱导的鼻咽癌cne-2细胞裸鼠移植瘤生长抑制作用的影响

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1、吗啡对顺铂诱导的鼻咽癌CNE-2细胞裸鼠移植瘤生长抑制作用的影响作者：操隆辉周建华林文前谭红鹰曾维安曾益新【摘要】【目的】以人鼻咽癌CNE-2细胞裸鼠移植瘤为模型，探讨吗啡对顺铂抑制肿瘤生长作用的影响及其机制。【方法】建立CNE-2细胞裸鼠移植瘤模型20只，随机分为4组，对照组，单纯顺铂用药组、单纯吗啡用药组和吗啡联合顺铂用药组，每组5只。吗啡5mg/kg每天给药1次，顺铂3mg/kg每3d给药2次，均为腹腔注射。用药14d后处死动物，完整剥离肿瘤，记净瘤质量。TUNEL染色计算细胞凋亡数，免疫组化染色检测肿瘤组织Bax，Bcl-2，cleaved-c

2、aspase-3以及CD34的表达情况。【结果】单纯顺铂用药组的瘤质量明显小于其它3组(P<0.05)，吗啡联合顺铂用药组的瘤质量明显小于对照组(P<0.05);TUNEL染色及cleaved-caspase-3染色显示单纯顺铂用药组的凋亡细胞数明显多于其他3组(P<0.05)。单纯顺铂用药组与其他3组相比Bax蛋白表达量增多，而Bcl-2表达量减少，单纯吗啡组的Bcl-2表达最强。CD34微血管染色显示单纯顺铂用药组的微血管密度显著少于其它3组(P<0.05)，单纯吗啡用药组的微血管密度显著多于对照组(P<0.05)。【

3、结论】吗啡通过拮抗顺铂诱导细胞凋亡及促进CNE-2细胞裸鼠移植瘤组织的血管生成，抵抗了顺铂抑制肿瘤生长的作用。14【关键词】吗啡;顺铂;凋亡;CNE-2细胞　Abstract：【Objective】Toevaluatetheeffectofmorphine(Mor)onthesuppressionofcisplatinontumorgrowthofhumannasopharyngealcarcinomaCNE-2xenograftsinnudemiceandpossiblemechanisms.【Methods】TwentyBALB/Cnudemice

4、weredividedinto4groupsrandomlyincludingcontrolgroup(0.01mL/gsalinewasgiveneveryday)，CDDPalonegroup(3mg/kgtwiceevery3days)，Moralonegroup(5mg/kgoncedaily)andthecombinationofMor(5mg/kgoncedaily)andCDDP(3mg/kgonceevery2days).Theprocedurelasted14daysafterbeginningtogivedrugs.Attheend

5、points，micewereeuthanizedandtumorweightswererecorded.TUNELstainingofCNE-2xenografttumorsectionswasusedfordetectingapoptosiscell.CD34，cleaved-caspase-3，Bcl-2andBaximmunohistologicstainingofthesametumorsectionswerealsoobserved.【Results】ThetumorweightofCDDPgroupwasthesmallestinallg

6、roups(P<0.05).ThetumorweightoftheMorandCDDPcombinationgroupwassmallerthanthatofthecontrolgroup.ThenumberofTUNEL-positiveandcleaved-caspase-3-positivecellsofCDDPgroupwerethemostinallgroup(P<0.05).ComparedwiththeothergroupsincludingtheMorandCDDPcombinationgroup，14theproteinB

7、axofCDDPgroupwasexpressedthehighestlevel，whereasthelevelofBcl-2wasthelowest.ThelevelofofBcl-2ofMorgroupwasthehighestinallgroup.TheexpressionofCD31decreasedafterCDDPtreatment，butincreasedaftermorphinetreatment.【Conclusion】Morphineinhibitedthesuppressionofcisplatinontumorgrowththr

8、oughinhibitingcisplatin-inducedapoptosisandprom