狼毒乙醇提取物限制糖脂代谢阻止小鼠肺癌细胞生长和转移  

Ethanol Extract fromStellera chamaejasme Prevent Lung Cancer Growth and Metastasis by Limiting Glucose and Lipid Metabolism

作　　者：林海红[1] 郭珍珍[1] 马小方[1] 曹宁[1] 杜钢军[1] 

机构地区：[1]河南大学药学院药物研究所,河南开封475004

出　　处：《河南大学学报（自然科学版）》2016年第4期414-421,共8页Journal of Henan University:Natural Science

基　　金：国家自然科学基金项目(81173094)

摘　　要：采用不同浓度的狼毒乙醇提取物处理体外培养的Lewis肺癌细胞48h,MTT法检测细胞粘附与增殖,transwell小室检测细胞运动,并测定细胞内葡萄糖(Glu)、葡萄糖转运体1(GLUT1)、游离脂肪酸(FFA)和甘油三酯(TG)水平.将小鼠Lewis肺癌细胞分别注射到小鼠腋部皮下和尾静脉建立小鼠Lewis肺癌皮下移植模型和实验性肺转移模型,分成模型组、狼毒乙醇提取物高剂量组和低剂量组,模型建立后次日给药,治疗3周评价狼毒乙醇提取物的抗肿瘤和抗转移作用,检测瘤组织中GLUT1、乳酸脱氢酶(LDH)、琥珀酸脱氢酶(SDH)、FFA和TG水平,并采用免疫组化法比较肺转移肿瘤部位与非肿瘤部位GLUT1和脂肪酸合成酶(FAS)的差异.结果显示,狼毒乙醇提取物对体外培养的Lewis肺癌细胞呈剂量依赖性抑制其粘附、增殖和运动,能降低细胞内Glu,GLUT1,FFA和TG水平.与未治疗的模型小鼠比较,狼毒乙醇提取物呈剂量依赖性减缓肿瘤生长速度、阻止肿瘤转移、延长荷瘤小鼠存活时间.狼毒乙醇提取物能降低瘤组织中GLUT1,LDH,FFA和TG水平,但增加SDH活性.在免疫组化中,与正常肺组织比较,狼毒乙醇提取物也能抑制肺转移肿瘤部位的GLUT1和FAS.以上结果表明,狼毒乙醇提取物能限制肿瘤细胞对葡萄糖和脂肪的利用从而阻止肺癌细胞的生长和转移,是一种有前景的新型潜在抗肿瘤药物.After the LLC cells were treated with different dose of EEC for 48 h, cell attachment and proliferation were examined by MTT assay, and transwell was used to detect cell motive and to measure the levels of cellular glucose （Glu）, glucose transporter 1 （GLUT1）, triglyceride （TG） and free fatty acids （FFA）. The LLC ceils were injected into the lateral axilla and tail vein respectively to produce LLC subcutaneous allograft and experimental lung metastasis. The tumor inocubating mice were randomized into model group, high dose EEC-treated group and low dose EEC-treated group. The mice received treatment for 3 weeks following tumor inocubation; the effects of EEC on tumor size and metastasis were evaluated; the levels of GLUT1, lactate dehydrogenase （LDH）, succinate dehydrogenase （SDH）, TG and FFA in tumor tissues were detected; the GLUT1 and fatty acid synthase （FAS） in lung region with tumor or not were compared by immunohistochemistry. Results show that EEC suppressed cell attachment and proliferation as well as cell motive in a dose dependent manner in LLC cells in vitro, which could decrease the levels of cellular Glu, GLUT1, TG and FFA. Compared with untreated model mice, EEC reduced tumor size and metastasis and prolongated life span in a dose dependent manner. EEC was able to decrease the levels of GLUT1, LDH, TG and FFA,but promote SDH activity in tumor tissues. In immunohistochemistry, EEC could inhibit GLUT1 and FAS in lung region with tumor. It is concluded that EEC could reduce tumor size and metastasis by limiting the utilization of glucose and lipid in LLC and might be an attractive antitumor agent with a novel mechanism.

关 键 词：狼毒乙醇提取物 糖代谢 脂肪代谢 LEWIS肺癌 转移 

分 类 号：R96[医药卫生—药理学]