摘要
目的 研究2-甲氧基雌二醇脂质体腹腔给药对S180腹水瘤的抑瘤效果。方法 建立S180腹水瘤昆明小鼠模型,随机分为6组,每组20只,雌雄各半,分别为阴性对照组、阳性对照组、2-甲氧基雌二醇溶液组、2-甲氧基雌二醇脂质体高、中、低剂量治疗组。连续腹腔给药7 d,每2 d测量腹围,观察荷瘤鼠行为体征,7 d后每组随机抽取半数荷瘤小鼠,颈椎脱臼处死,解剖观察腹腔中主要脏器、称重,取出肝脏用中性甲醛固定,常规切片进行病理检查,收集腹水,测量体积,计算细胞存活率,流式细胞术检测肿瘤细胞周期及凋亡率的变化,剩余小鼠统计生存时间,计算生命延长率。结果 2-甲氧基雌二醇脂质体各治疗组小鼠平均生存时间明显延长。治疗组腹水量降低,腹水中癌细胞存活率下降,病理切片结果显示,癌细胞较少在腹腔内转移。结论 腹腔注射2-甲氧基雌二醇脂质体可抑制S180细胞生长并减少腹水形成,对腹水引起的腹腔转移癌有治疗作用,并显示出剂量依赖性,脂质体治疗效果优于溶液组。
Abstract
OBJECTIVE To investigate the inhibition of 2-methoxyestradiol liposomes on S180 ascites tumor in mice. METHODS 120 Kunming mice with ascites tumor were distributed into six groups at random:control group, 5-fluorouracil group, 2-methoxyestral solution, 2-methoxyestradiol liposomes 30.0, 22.5, 15.0 mg·kg-1·d-1 groups. All the treatments were given for 7 d and the interval was 24 h. The abdomen circumference of the mice were recorded in all groups every two days. Ascites volume inhibition and cell persistence of mice were evaluated as well as the cell cycle and apoptosis. The pathologica changes of liver were observed by optical microscope. RESULTS Mice in treated groups attained longer survival time, ascites volume inhibition and lower cell persistence. CONCLUSION Intraperitoneal administration of 2-methoxyestradiol liposome is effective for the treatment of S180 ascites mice, and could inhibite metastasis of ascites cell in abdominal cavity. The curative effect of 2-ME liposome is dose-dependent.
关键词
2-甲氧基雌二醇 /
S180腹水瘤 /
脂质体 /
药效学
{{custom_keyword}} /
Key words
2-methoxyestradiol /
S180 ascites tumor /
liposome /
pharmacodynamics
{{custom_keyword}} /
杜斌 李晓天 王舒雨 赵芝兰 赵娅 张振中.
2-甲氧基雌二醇脂质体对S180腹水瘤的抑瘤作用研究[J]. 中国药学杂志, 2010, 45(16): 1233-1237
DU in;LI Xio-tin;WNG Shu-yu;ZHO Zhi-ln;ZHO Y;ZHNG Zhen-zhong.
OBJECTIVE To investigate the inhibition of 2-methoxyestradiol liposomes on S180 ascites tumor in mice. METHODS 120 Kunming mice with ascites tumor were distributed into six groups at random:control group, 5-fluorouracil group, 2-methoxyestral solution, 2-methoxyestradiol liposomes 30.0, 22.5, 15.0 mg·kg-1·d-1 groups. All the treatments were given for 7 d and the interval was 24 h. The abdomen circumference of the mice were recorded in all groups every two days. Ascites volume inhibition and cell persistence of mice were evaluated as well as the cell cycle and apoptosis. The pathologica changes of liver were observed by optical microscope. RESULTS Mice in treated groups attained longer survival time, ascites volume inhibition and lower cell persistence. CONCLUSION Intraperitoneal administration of 2-methoxyestradiol liposome is effective for the treatment of S180 ascites mice, and could inhibite metastasis of ascites cell in abdominal cavity. The curative effect of 2-ME liposome is dose-dependent.
[J]. Chinese Pharmaceutical Journal, 2010, 45(16): 1233-1237
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] TARA E S, ROBIN L A, RICHARD A H, et al. 2-Methoxyestradiol-a unique blend of activities generating a new class of anti-tumour/anti-inflammatory agents [J]. J Biol Chem, 2007, 12 (13-14): 577-584.
[2] RAJENDRA B, YESIM G P, GEORGE W, et al. 2-Methoxyestradiol inhibits the anaphase-promoting complex and protein translation in human breast cancer cells [J]. Cancer Res, 2007,67 (2):702-708.
[3] BOULIKAS T. Low toxicity and anticancer activity of a novel liposomal cisplatin (lipolatin) in mouse xenografts [J]. Oncol Rep, 2004,43 (20):3-12.
[4] TORCHILIN V P, ANWER M K, TALEGANONKAR S, et al. Recent advances with liposomes as pharmaceutical carriers [J]. Nat Rev Drug Discov, 2005,4(5):145-160.
[5] CHEN N, YANG M, QIAN X P, et al. Antitumor effects of paclitaxel-loaded liposome on S180 ascites-tumour bearing mice [J]. J Nanjing Med Univ (南京医科大学学报), 2007,27(7):706-710.
[6] DU B, LI Y, LI X T, et al. Preparation, characterization and in vivo evaluation of 2-methoxyestradiol-loaded liposomes [J]. Int J Pharm, 2010, 384(1-2): 140-147.
[7] JI Y B, QU Z Y, ZOU X, et al. Studies on Inhibition of juglone in exocarpium juglandis immaturum on S180 sarcoma in mice [J]. Chin Pharm J (中国药学杂志), 2009,44 (3):195-199.
[8] LU Y, HOU S X, LI Y, et al. Evaluation of inhibition activity of VCR transfersomes on burkitt′s lymphoma in nude mice [J]. Chin Pharm J (中国药学杂志), 2008,43 (12):910-913.
[9] CHEN L C, CHANG C H, YU C Y, et al. Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy 188Re-DXR-liposome in C26 colon carcinoma ascites mice model [J]. Nuc Med Biol, 2008,16(34):883-893.
[10] JING X H, ZHANG C Z, WANG Y F, et al . The effect of panaxoside-Rg3 in the treatment on ascitic-fluid type hepatocarcinoma H22 in mice [J]. Chin Clin Oncol (临床肿瘤学杂志), 2007,12 (7):522-525.
[11] CHEN T. Rhizoma panacis majori reduces toxicity of chemotherapy in S180-bearing mice [J]. J Chin Integr Med (中西医结合学报), 2008,6 (12):1255-1258.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}