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  

Effect of Morphine on Suppression of Cisplatin on Tumor Growth of Human Nasopharyngeal Carcinoma CNE-2 Xenografts in Nude Mice

作　　者：操隆辉[1] 周建华[2] 林文前[1] 谭红鹰[1] 曾维安[1] 曾益新[3] 

机构地区：[1]华南肿瘤学国家重点实验室//中山大学肿瘤防治中心麻醉科,广东广州510060 [2]华南肿瘤学国家重点实验室//中山大学肿瘤防治中心超声科,广东广州510060 [3]华南肿瘤学国家重点实验室//中山大学肿瘤防治中心实验研究部,广东广州510060

出　　处：《中山大学学报（医学科学版）》2010年第3期371-375,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(303041102002)

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-caspase-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)。【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。【Objective】To evaluate the effect of morphine（Mor）on the suppression of cisplatin on tumor growth of human nasopharyngeal carcinoma CNE-2 xenografts in nude mice and possible mechanisms.【Methods】Twenty BALB/C nude mice were divided into 4 groups randomly including control group（0.01 mL/g saline was given every day）,CDDP alone group（3 mg/kg twice every 3 days）,Mor alone group（5 mg/kg once daily）and the combination of Mor（5 mg/kg once daily）and CDDP（3 mg/kg once every 2 days）.The procedure lasted 14 days after beginning to give drugs.At the end points,mice were euthanized and tumor weights were recorded.TUNEL staining of CNE-2 xenograft tumor sections was used for detecting apoptosis cell.CD34,cleaved-caspase-3,Bcl-2 and Bax immunohistologic staining of the same tumor sections were also observed.【Results】The tumor weight of CDDP group was the smallest in all groups（P0.05）.The tumor weight of the Mor and CDDP combination group was smaller than that of the control group.The number of TUNEL-positive and cleaved-caspase-3-positive cells of CDDP group were the most in all group（P0.05）.Compared with the other groups including the Mor and CDDP combination group,the protein Bax of CDDP group was expressed the highest level,whereas the level of Bcl-2 was the lowest.The level of of Bcl-2 of Mor group was the highest in all group.The expression of CD31 decreased after CDDP treatment,but increased after morphine treatment.【Conclusion】Morphine inhibited the suppression of cisplatin on tumor growth through inhibiting cisplatin-induced apoptosis and promoting angiogenesis of human CNE-2 xenografts in nude mice.

关 键 词：吗啡 顺铂 凋亡 CNE-2细胞 

分 类 号：R739.6[医药卫生—肿瘤]