榄香烯联合5-FU体内外抑制人胃癌MGC80-3细胞增殖与诱导凋亡作用的研究Antitumor Effects of Elemene Combined with Fluorouracil on Proliferation Inhibition and Apoptosis Induction in Human Gastric Cancer Cell Line MGC80-3
陈雨,王茜莎,韩重,杨威,周云,党靖涛
CHEN Yu,WANG Xisha,HAN Zhong,YANG Wei,ZHOU Yun,DANG Jingtao
摘要(Abstract):
目的研究中药莪术提取物榄香烯制剂(Elemene)联合5-氟尿嘧啶(5-FU)对MGC80-3细胞增殖的抑制及诱导凋亡的作用。方法采用MTT法考察榄香烯、5-FU单药及联合作用于MGC80-3细胞的体外抗肿瘤效应;应用中效原理进行统计分析单药及联合用药对肿瘤细胞生长的影响,确定联合用药时的效应(Fa)合用指数(CI)的关系;流式细胞仪检测细胞凋亡周期改变。通过建立MGC80-3裸鼠体内异种肿瘤模型,考察榄香烯及5-FU单用及合用对荷瘤小鼠肿瘤生长的抑制作用。结果体外试验结果表明榄香烯与5-FU联合应用作用于MGC80-3细胞可产生较好协同效应,单染法(PI)检测到榄香烯与5-FU联合之后能够使MGC80-3细胞表现出显著的G0/G1期阻滞作用;体内试验结果表明榄香烯单药及与5-FU联合作用对MGC80-3裸鼠异种肿瘤生长均有明显的抑制作用,且联合用药组抑瘤率可达84.68%。结论榄香烯联合5-FU作用于MGC80-3肿瘤细胞株可产生较好的协同效应。
OBJECTIVE To investigate the antitumor effects of elemene combined with fluorouracil on the proliferation inhibition and apoptosis induction in human gastric cancer. METHODS The synergistic interaction on human gastric cancer was evaluated by using MTT and the combination index( CI) method. The median-effect principle was used to analyze the relationship of Fa-CI by drawing growth curves of alone / combination effects on tumor cells; The cell cycle and apoptosis were observed by flow cytometry. Nude mouse models of the solid tumor of gastric cancer were established. The inhibitory rates of solid tumor were observed by elemene and fluorouracil alone and in combination therapy. RESULTS Elemene appeared a promising candidate for combination with fluorouracil in cancer chemotherapy and the combination showed significant G0 / G1 arrest. Growth of cells was significantly inhibited in a dose and reaction time dependent manner which were treated with various concentrations of drug. The combination group suppressed the most obviously tumor growth. CONCLUSION When elemene combined with fluorouracil,elemene has synergetic effect in inhibiting the proliferation of gastric cancer cells.
关键词(KeyWords):
榄香烯;胃癌;中效原理;协同作用;凋亡
elemene;gastric cancer;the work principle;synergistic effect;apoptosis
基金项目(Foundation): 国家十二五科技重大专项项目(2013ZX09103001012)
作者(Author):
陈雨,王茜莎,韩重,杨威,周云,党靖涛
CHEN Yu,WANG Xisha,HAN Zhong,YANG Wei,ZHOU Yun,DANG Jingtao
参考文献(References):
- [1]曹海滨,黄继英,时宝忆,等.上海市青浦区2002年-2008年新发胃癌患者队列生存分析[J].中国临床医学,2010,17(6):826.
- [2]孙秀娣,牧人,周有尚,等.中国胃癌死亡率20年变化情况分析及其发展趋势预测[J].中华肿瘤杂志,2004,26(1):4.
- [3]鲁露,李争光,吴昌平,等.鱼藤素和氟尿嘧啶对胃癌细胞株MGC80-3的协同抗肿瘤作用[J].肿瘤学杂志,2013,19(7):523-526.
- [4]赵亚利,彭晓霞,王亚东,等.榄香烯注射液治疗肺癌的有效性与安全性评价[J].中国循证医学杂志,2005,5(3):216.
- [5]王宝成,郭军,狄剑时,等.榄香稀注射液乳剂与肿瘤多药耐药的基础研究[J].中国肿瘤临床,1996,23(2):143.
- [6]Li QQ,Wang G,Zhang M,et al.Beta-Elemene,a novel plantderived antineoplastic agent,increases cisplat in chemosensitivity of lung tumor cells by triggering apoptosis[J].Oncol Rep,2009,22(1):161-170.
- [7]Xie CY,Yang W,Li M,et al.Cell apoptosis induced by deltaelemene in co-lorectal adenocarcinoma cells viaam itochondrialmediated pathway[J].Yakugaku Zasshi,2009,129(11):1403-1413.
- [8]邹征云,魏嘉,王婷婷,等.藤黄酸与5-FU相互作用的中效原理评价[J].中华肿瘤防治杂志,2009,8(16):1225-1227.
- [9]许文翠,任双义.榄香烯联合氟尿嘧啶对肝癌H22荷瘤小鼠的抑瘤作用[J].中国临床药学杂志,2011,20(5):270-273.
- [10]李学,贾立群,程志强,等.榄香烯及5-氟脲嘧啶生化调节方案治疗胃肠道腺癌临床疗效观察[J].中日友好医院学报,2004,18(1):6-9.
- [11]刘静,李朝晖,刘云鹏,等.β-榄香烯对胃癌MGC803细胞凋亡的影响及机制探讨[J].山东医药,2011,51(14):1-2.
- [12]韦尉元,吴琨,王晓通,等.5-FU联合人参黄芪复方对人胃癌MGC80-3细胞生物学行为的影响[J].中国中西医结合杂志,2012,32(12):1647-1651.
- [13]Vermesi,Hannen C,Steffens-nakken H,et al.A novel assay for apoptosis.Flow cytometrie detection of phasphatidylserine expression on early apoptotic cells using flourescein labeled Annexin V[J].Immunol Methods,1995,184:39-51.
- [14]季娜,张红.榄香烯体内外抑制小鼠肝癌H22细胞增殖与诱导凋亡作用的研究[J].中国中西医结合消化杂志,2011,19(2):97-100.