青蒿琥酯对腺样囊性癌NACC细胞裸鼠移植瘤抑制效果的研究  

Inhibition Effects of Artesunate on Human Palatal Salivary Gland Cell Line of Adenoid Cystic Carcinoma in Vivo

作　　者：胥航[1] 农晓琳[1] 李异兴[1] 李佳荃[2] 俞立平[1] 朴智[1] 

机构地区：[1]广西医科大学口腔医学院,南宁530021 [2]广西医科大学医学科学实验中心,南宁530021

出　　处：《世界科学技术-中医药现代化》2013年第2期222-227,共6页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金项目(30060082):腺样囊性癌神经血管侵袭性与生长因子及受体关系的研究;负责人:农晓琳;教育部"春晖计划"科研启动基金项目(教外司留[2003]593-7):腺样囊性癌神经血管侵袭性与癌基因关系的研究;负责人:农晓琳;广西自然科学基金重点项目(2010GXNSFD013047):靶向抑制CXCR4对腺样囊性癌干细胞样细胞生物学特性的影响及其机制;负责人:农晓琳;广西科学基金(桂科回0836013):口腔颌面部癌干细胞研究;负责人:农晓琳;广西卫生厅重点科研项目(重200006):腺样囊性癌沿神经血管侵袭转移的临床及生物学基础研究;负责人:农晓琳;广西卫生厅重点科研项目(重200927):重组shRNA质粒抑制NGF;VEGF在腺样囊性癌中表达的研究;负责人:农晓琳;广西研究生教育创新计划项目(2011105981003M184):靶向抑制趋化因子受体4对具有干细胞表型舌鳞状细胞癌耐药细胞生长及耐药性的影响;负责人:胥航

摘　　要：目的:观察青蒿琥酯(ART)对腺样囊性癌裸鼠移植瘤的治疗效果,并探讨其作用机制。方法:裸鼠背部皮下接种涎腺腺样囊性癌NACC细胞系,建立移植瘤模型,接种7天后始见成瘤时,随机将动物分为5组,即生理盐水对照组、ART 50.0 mg.kg-1组、ART 100.0 mg.kg-1组、ART 200.0 mg.kg-1组、DDP 2.0 mg.kg-1组。每组5只,隔天给药,称裸鼠体重,给药8次后取瘤称重,采用免疫组化法、Western blot法检测Bcl-2,ERK2,VEGF的表达。结果:ART 200.0 mg.kg-1组以及DDP 2.0 mg.kg-1组移植瘤瘤重较生理盐水对照组明显减轻(P<0.05)。ART 200.0 mg.kg-1组与DDP 2.0 mg.kg-1组相比,抑瘤效果无显著性差异(P>0.05)。DDP 2.0 mg.kg-1组体重减轻明显,极度瘦弱,其余各组体重及生活状态无明显改变。瘤体标本免疫组化及Western blot法检测均发现ART 100.0 mg.kg-1可引起细胞凋亡并下调Bcl-2、ERK2以及VEGF的表达,这种下调作用在ART 200.0 mg.kg-1组更为明显,其与DDP 2.0 mg.kg-1组效果相似。结论:青蒿琥酯可有效抑制腺样囊性癌裸鼠移植瘤的生长,且毒副作用小,其作用机制可能与下调肿瘤VEGF,Bcl-2,ERK2的表达相关。This study was aimed to investigate treatment effects of artesunate （ART） on a palatal salivary gland cell line of adenoid cystic carcinoma named NACC in vivo. NACC cells were inoculated subcutaneously into BABL-C nude mice. The xenografting mice were divided into the control group, increasing dose of ART treated groups and DDP treated group. Treatments started on the 7~ day when solid tumors were palpated. Drugs were given every other day for 8 times. The animals were sacrificed on the 23^th day. And then, tumors were excised and weighted. Tumors were also investigated by immunohistochemistry and Western blotting. The results showed that xenograft of athymic nude mouse were significantly inhibited by ART 200 mg/kg and DDP 2.0 mg/kg （P 〈 0.05） in vivo. ART 200 mg .kg^-1 and DDP 2.0 mg-kg-l had the same effects in suppressing the growth of nude mice xenograft. With the increasing of ART concentration, the expression of VEGF, Bcl-2 and ERK2 had been down-regulated in transplanted tumors, especially in ART 100 mg.kg^-1, ART 200 mg.kg^-1 and DDP 2.0 mg .kg^-1 groups （P 〈 0.05）. It was concluded that ART could significantly inhibit the growth of NACC cell athymic mice xenograft. The mechanism might related to tumor growth-inhibiting, apoptosis-inducing and neo- vascularizationsuppressing.

关 键 词：青蒿琥酯 腺样囊性癌 裸鼠移植瘤 抑瘤率 

分 类 号：R285[医药卫生—中药学]