新型有机硒化合物Eb抗肿瘤, 免疫活性及硒组织分布特点

新型有机硒化合物Eb抗肿瘤, 免疫活性及硒组织分布特点

严俊, 邓声菊, 况斌, 贺飞, 刘涛, 曾慧慧^*

北京大学药学院, 北京 100083

收稿日期:2004-04-21 修回日期:2004-08-10 出版日期:2004-09-15 发布日期:2004-09-15
通讯作者: 曾慧慧*

Selenium Distribution Pattern, Antineoplastic and Immunostimulatory Activities of a Novel Organoselenium Compound Eb

YAN Jun, DENG Sheng-ju, KUANG Bin, HE Fei, LIU Tao, ZENG Hui-hui^*

School of Pharmaceutical Sciences, Peking University, Beijing 100083, China

Received:2004-04-21 Revised:2004-08-10 Online:2004-09-15 Published:2004-09-15
Contact: ZENG Hui-hui*

摘要/Abstract

摘要： 目的研究新型有机硒化合物Eb的组织分布特点、体外抗肿瘤及免疫活性,同时对其体内的抗肿瘤前景进行探讨. 方法昆明种小鼠连续灌胃给药Eb后, 用荧光法测定心、肝、脾、肾、肺、胃、脑、肌、骨组织的硒含量,来考察Eb组织分布特异性. 用MTT法检测其体外抗肿瘤活性.用淋巴细胞转化,溶血素抗体生成实验及吞噬细胞吞噬实验检测其免疫活性. 结果连续灌胃Eb治疗剂量(0.1 g·kg^-1·d^-1)7天后,肝、脾、肺、肾、骨组织的硒含量增高,其中肝、脾组织的硒含量增高显著.心、胃、脑、肌肉组织的硒含量基本没变化; Eb对体外培养的人肝癌Bel-7402细胞、胃癌BGC-823细胞、肺癌Calu-3细胞具有生长抑制作用; Eb具有促进淋巴细胞转化、溶血素抗体生成及增强吞噬细胞吞噬功能的作用. 结论 Eb具有体外抗肿瘤, 免疫增强活性及在肝、脾、肺、肾、骨组织的靶向性蓄积作用, 表明Eb有作为抗肝、肺、肾、骨等组织肿瘤及增强免疫功能药物进一步研究的意义.

关键词: 有机硒化合物, 有机硒化合物, 有机硒化合物, 组织分布, 组织分布, 组织分布, 抗肿瘤活性, 抗肿瘤活性, 抗肿瘤活性, 免疫活性, 免疫活性, 免疫活性

Abstract: Aim To study the distribution pattern, antineoplastic activity and immunocompetence of a novel organoselenium compound Eb and investigate its in vivo antineoplastic potential. Methods Eb was administered to Kunming mice (dosage, 0.1 g·kg^-1·d^-1) intragastrically for 7 successive days. The contents of selenium in heart, liver, spleen, kidneys, lungs, stomach, brain, muscle, and bone were determined by fluorometric method on the eighth day. MTT assay was used to study tumor growth inhibition of Eb in vitro, and lymphocyte transformation, hemolysin formation and phagocytosis assay were used to study its immunocompetence. Results After 7 days, administration of Eb, the tissue contents of sele-(nium) in liver, spleen, lungs, kidneys, and bone of mice increased, especially those in liver and spleen increased significan-tly, compared with controls; but no significant changes of such contents were found in muscle, heart, brain, and stomach. Eb demonstrated inhibitory effects on human Bel-7402, BGC-823, and Calu-3 cancer cell lines in vitro. Eb also showed ability to enhance lymphocyte transformation and serum hemolysin formation in vitro and increase the phagocytosis of macrophages. Conclusion The validated antitumor and immunostimulatory activities of Eb suggest a hypothesis that Eb may behave as a biological response modifier when used as an antitumor agent. Eb is worthy of further study in developing a new antineoplastic and immunity enhancing agent in the light of its antitumor activity, immunocompetence and specific distribution in liver, lungs, kidneys, bone, and spleen.

Key words: Organoselenium compound, Organoselenium compound, tissue distribution, tissue distribution, antitumoral activity, antitumoral activity, immunocompetence, immunocompetence

中图分类号:

R962

R979.1

Supporting: Foundation item: Natural Science Foundation of Beijing (7021001); The Foundation for the Special Program of the Following Novel Candidate Drug by Beijing S&T Committee (H020220060190).
^*Corresponding author. Tel.: 86-10-82802878; fax: 86-10-62015584

严俊, 邓声菊, 况斌, 贺飞, 刘涛, 曾慧慧^*. 新型有机硒化合物Eb抗肿瘤, 免疫活性及硒组织分布特点[J]. .

YAN Jun, DENG Sheng-ju, KUANG Bin, HE Fei, LIU Tao, ZENG Hui-hui^*. Selenium Distribution Pattern, Antineoplastic and Immunostimulatory Activities of a Novel Organoselenium Compound Eb[J]. .

参考文献

[1] Das A, Desai D, Pittman B, et al. Comparison of the chemopreventive efficacies of 1,4-phenylenebis (methylene) selenocyanate and selenium-enriched yeast on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced lung tumorigenesis in A/J mouse [J]. Nutr Cancer, 2003, 46: 179-185.
[2] Schrauzer GN. Cancer mortality correlation studies-III: statistical associations with dietary selenium intakes [J]. Bioinorg Chem, 1977, 5: 23-24.
[3] Wang L, Ling R,Geng J. The distribution and meaning of trace element selenium and oxygen radical in primary breast cancer [J]. J Fourth Milit Med Univ, 1995, 16 (1): 15-15.
[4] Musik I, Koziol-Montewka M, Tos-Luty S, et al. Comparison of selenium distribution in mice organs after the supplementation with inorganic and organic selenium compound selenosemicarbazide [J]. Ann Univ Mariae Curie Sklodowska, 2002, 57: 15-22.
[5] Jastrzebski Z, Czyzewska-Szafran H, Remiszewska M, et al. Pharmacokinetics of selol, a new agent containing selenium in rats [J]. Drugs Exp Clin Res, 1997, 23: 7-11.
[6] Liu Q, Analysis and determination of selenium [A]. In: Xu HB, Huang KX, ed. Selenium: Its chemistry, biochemistry and application in life science [M]. Wuhan: Publishing House of Huazhong Science and Technology University, 1994. 80-86.
[7] Tang QH, Sun Y, Zhou JM, et al. Determination of selenium in serum by 2,3-diaminonaphthalene fluoroscopy[J]. Clin Inspec, 1994, 12: 186-187.
[8] Shi CJ, Yu LZ, Yang FG, et al. A novel organoselenium compound induces cell cycle arrest and apoptosis in prostate cancer cell lines [J]. Biochem Biophys Res Commun, 2003, 309: 578-583.
[9] Wang YR, Zeng HH. The investigation of anticarcinogenic action of BBSKE, a novel organoselenium compound, in inhibiting on growth and metastasis of surgically transplanted Lewis lung cancer [J]. J Peking Univ (Health Sci), in press.
[10] Shi CJ, Zeng HH, Li HW, et al. Induction of apoptosis in prostate cancer cell line PC-3 by BBSKE, a novel organoselenium compound, and its effect in vivo [J]. Natl Med J China, 2003, 83: 1984-1988.

[1]	许士琪, 朱礼岩, 郝超, 刘文倩, 陈成龙, 陈泳怡, 刘爱芹. 一种新型含氨基酸基团替加氟前药的合成及其抗肿瘤活性评价[J]. 中国药学(英文版), 2021, 30(9): 743-753.
[2]	周北斗, 俞紫涵, 童玉贵, 李佳莉, 黄堡城, 魏蓉蓉, 翁智敏, 王欣, 阮志鹏, 林健, 许彩红, 刘建波. 异戊烯基和香叶基取代的呫吨酮的合成与生物活性研究[J]. 中国药学(英文版), 2020, 29(8): 564-576.
[3]	雷丽, 陈宇, 杨思敏, 孟祥豹, 余四旺. 一个新型氮杂萘醌类化合物通过诱导细胞凋亡来抑制肿瘤生长[J]. 中国药学(英文版), 2018, 27(9): 600-607.
[4]	吴珍珍, 任恒春, 李艳英, 付佳佳, 刘晓俊, 胡杰. 外用及口服马钱子碱囊泡凝胶在大鼠体内的组织分布和药物动力学研究[J]. 中国药学(英文版), 2018, 27(2): 92-98.
[5]	梁晓霞, 孔令茜, 何敏. 从卵叶蜘蛛抱蛋中分离得到的一个具有潜在抗菌活性的高异黄酮类化合物[J]. 中国药学(英文版), 2016, 25(9): 700-703.
[6]	周代营, 赵肃清, 郑希, 杜志云, 张焜. 哌啶酮类姜黄素类似物的合成及抗肿瘤活性研究[J]. 中国药学(英文版), 2015, 24(8): 524-529.
[7]	鞠爱霞, 康宇红, 薛清丹, 李秋红. 汉防己甲素在大鼠体内的药代动力学、组织分布和排泄研究[J]. 中国药学(英文版), 2015, 24(8): 557-562.
[8]	郭亮, 范文玺, 甘紫云, 陈伟, 马芹, 曹日晖. 1-取代-β-咔啉衍生物的设计、合成与初步的抗肿瘤作用研究[J]. 中国药学(英文版), 2015, 24(12): 801-808.
[9]	夏玉凤^*, 戴岳, 梁惠贞. 大鼠口服东莨菪素后的组织分布和排泄特征研究[J]. , 2012, 21(2): 149-155.
[10]	李叶桓, 张国州, 黄荣华, 李冬冬, 罗钰, 杨勇, 吴银群, 刘丽慧, 曾慧慧^*. 新型有机硒类抗肿瘤化合物WB硒啉在体内组织分布研究[J]. , 2011, 20(6): 578-583.
[11]	闫冲, 林励^*, 刘红菊, 张延娇, 陈雅慧. HPLC研究异牡荆苷在大鼠体内的药代动力学及组织分布[J]. , 2011, 20(4): 376-382.
[12]	李功, 孙崎^, 崔景荣, 李润涛^. 螺环季铵盐修饰的苯丁酸氮芥类抗肿瘤化合物[J]. , 2010, 19(5): 346-352.
[13]	章俊麟, 金武, 王学清, 王坚成, 张烜, 张强^*. 奥曲肽修饰的PEG隐形脂质体用于改善阿霉素对生长抑素受体II阳性肿瘤的抗癌效果[J]. , 2010, 19(5): 363-370.
[14]	王金萍, 祝侠丽, 席延伟, 王德凤, 黄桂华^*. 洛莫司汀脂质体的制备及药代动力学和组织分布学研究[J]. , 2010, 19(5): 353-362.
[15]	傅佳凝, 王静瑜, 王立辉, 王磊, 唐菀晨, 蔡高雄, 刘密, 曾慧慧^*. 国家一类抗肿瘤新药有机硒化合物乙烷硒啉的药效药理作用[J]. , 2010, 19(3): 163-168.