高级脂肪酸类似物的合成及抗肿瘤作用的研究
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摘要
目的:对高级脂肪酸进行结构修饰和改造,合成高级脂肪酸类似物;通过体外抗肿瘤实验,筛选出抗肿瘤活性化合物;将筛选出的活性化合物进行体内抗肿瘤作用及量效关系研究。
方法:1.对高级脂肪酸进行结构修饰和改造,合成纯化化合物并进行结构鉴定。2.体外抗肿瘤活性筛选:选择人舌癌、人卵巢癌等细胞,研究对肿瘤细胞的杀伤率,筛选出活性化合物。3.将筛选出的化合物做体内抗肿瘤作用研究:将S180细胞接种到昆明种小鼠腹腔,形成S180昆明种小鼠腹水肿瘤模型,考察给药组的生命延长率及体重变化情况,研究药物体内抗肿瘤作用及量效关系。
结果:1.对高级脂肪酸衍进行结构修饰和改造,合成了9个化合物并进行结构鉴定。2.体外实验筛选得化合物MDH332、MDH341、MDH342对癌细胞有明显杀伤作用,其中MDH341杀伤作用最强。3.进一步做体内实验证明,MDH341能延长S180型腹水肿瘤小鼠的生存时间,对S180昆明种小鼠腹水肿瘤治疗效果较好。
结论:体外实验证明,MDH332、MDH341、MDH342在抗肿瘤方面具有一定的应用前景,其中以MDH341抗肿瘤活性最强;体内试验证明,MDH341能显著延长S180型腹水肿瘤小鼠的存活时间。
Objective: To synthesize the analogues of high fatty acids by structural modification. To select anti-tumor active compounds through the anti-tumor testing in vitro. To study those compounds on their anti-tumor effect and dose-effect relationship in vivo.
Method: 1. To synthesize the analogues of high fatty acids by structural modification and elucidate their structures. 2. Anti-tumor activities in vitro selection: Choose one tongue cancer, ovarian cancer and other cells, flow cytometry application of compounds on the destruction of tumor cells, the activity of compounds in the screening. 3. Anti-tumor effect in vivo: S180 cells were to Kunming mice, a mouse ascites tumor model S180, research compounds in anti-tumor effects, study treatment group to extend the life of the rate and weight Change, and research carried out dose-effect relationship in vivo .
Results: 1. Eight designed compounds were synthesized and structural identified. 2. Three compounds MDH332, MDH341 and MDH342 have obvious anti-cancer active to cancer cells in vitro, MDH341 is strongest. 3. Further proof to do in vivo, MDH341 can extend the survival time of mice ascites tumor model S180.
Conclusion: In vitro proof, MDH332, MDH341, MDH342 in the anti-tumor has a certain prospect, MDH341 is strongest; in vivo proof , MDH341 can extend the survival time of mice ascites tumor model S180.
方法:1.对高级脂肪酸进行结构修饰和改造,合成纯化化合物并进行结构鉴定。2.体外抗肿瘤活性筛选:选择人舌癌、人卵巢癌等细胞,研究对肿瘤细胞的杀伤率,筛选出活性化合物。3.将筛选出的化合物做体内抗肿瘤作用研究:将S180细胞接种到昆明种小鼠腹腔,形成S180昆明种小鼠腹水肿瘤模型,考察给药组的生命延长率及体重变化情况,研究药物体内抗肿瘤作用及量效关系。
结果:1.对高级脂肪酸衍进行结构修饰和改造,合成了9个化合物并进行结构鉴定。2.体外实验筛选得化合物MDH332、MDH341、MDH342对癌细胞有明显杀伤作用,其中MDH341杀伤作用最强。3.进一步做体内实验证明,MDH341能延长S180型腹水肿瘤小鼠的生存时间,对S180昆明种小鼠腹水肿瘤治疗效果较好。
结论:体外实验证明,MDH332、MDH341、MDH342在抗肿瘤方面具有一定的应用前景,其中以MDH341抗肿瘤活性最强;体内试验证明,MDH341能显著延长S180型腹水肿瘤小鼠的存活时间。
Objective: To synthesize the analogues of high fatty acids by structural modification. To select anti-tumor active compounds through the anti-tumor testing in vitro. To study those compounds on their anti-tumor effect and dose-effect relationship in vivo.
Method: 1. To synthesize the analogues of high fatty acids by structural modification and elucidate their structures. 2. Anti-tumor activities in vitro selection: Choose one tongue cancer, ovarian cancer and other cells, flow cytometry application of compounds on the destruction of tumor cells, the activity of compounds in the screening. 3. Anti-tumor effect in vivo: S180 cells were to Kunming mice, a mouse ascites tumor model S180, research compounds in anti-tumor effects, study treatment group to extend the life of the rate and weight Change, and research carried out dose-effect relationship in vivo .
Results: 1. Eight designed compounds were synthesized and structural identified. 2. Three compounds MDH332, MDH341 and MDH342 have obvious anti-cancer active to cancer cells in vitro, MDH341 is strongest. 3. Further proof to do in vivo, MDH341 can extend the survival time of mice ascites tumor model S180.
Conclusion: In vitro proof, MDH332, MDH341, MDH342 in the anti-tumor has a certain prospect, MDH341 is strongest; in vivo proof , MDH341 can extend the survival time of mice ascites tumor model S180.
引文
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[6]秦箐,侯华新,邱莉等.板蓝根高极性流分及其亚流分抗氧自由基的活性.中国临床药学杂志.2001,10(6):373-375.
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[14]秦箐,侯华新,邱莉等.板蓝根高极性流分及其亚流分抗氧自由基的活性.中国临床药学杂志,2001,10(6):373-375.
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[23] Danbara N, Yuri T, Tsujita2KyutokuM, etal. Conjugated docosahexaenoic acid is a potent inducer of cell cycle arrest and apop tosis and inhibits growth of colo 201 human colon cancer cells [J].Nutr Cancer, 2004, 50 (1) : 71-79.
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[32]孙润广,张静,王永昌.脂肪酸多相脂质体与癌细胞膜相互作用的ESR谱研究.生物化学与生物物理进展. 200,27(3):296-300
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[35] Thompson H, Zhu Z, Banni S, et al. Morphological and Biochemical status and the mammary gland as influenced by conjugated linoleic acid: implycation for a reduction in mammary cancer risk [J]. cancer Res. 1997,57(22): 5067-5072.
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[2]秦箐,贺海平,Soren Brogger Christensen等.中药板蓝根中高级不饱和脂肪酸的分离鉴定及免疫活性成分的研究.中国现代医学杂志.2001,11(1):15-16.
[3]秦箐,贺海平,Soren Brogger Christensen等.板蓝根低极性流分的分离及其免疫活性.中国临床药学杂志.2001,10(1):29-31.
[4]秦箐,贺海平,Soren Brogger Christensen等.中药板蓝根中蓝色流分的分离及其对体外人多形核细胞化学发光的影响.广西医科大学学报.2001,18(2):196-197.
[5]秦箐,贺海平,Soren Brogger Christensen等.中药板蓝根两个高极性流分的分离及其活性的研究.中国药理学通报.2001,17(6):714-715.
[6]秦箐,侯华新,邱莉等.板蓝根高极性流分及其亚流分抗氧自由基的活性.中国临床药学杂志.2001,10(6):373-375.
[7]侯华新,秦箐,黎丹戎等.板蓝根高级不饱和脂肪组酸的体外抗人肝癌BEL-7402细胞活性.中国临床药学杂志,2002,11(1):16-19.
[8]侯华新,黎丹戎,韦长元等.板蓝根高级不饱和脂肪酸对耐药肝癌细胞株BEL-7404/ADM逆转作用实验.中国现代应用药学杂志.2002,19(5):351-353.
[9]侯华新,黎丹戎,秦箐等.板蓝根高级不饱和脂肪酸体内抗肿瘤实验研究.中药新药与临床药理.2002,13(3):156-157.
[10]韦长元,黎丹戎等.板蓝根组酸对耐药人肝癌原位移植瘤的耐药逆转研究.肝胆外科杂志.2004,12(5):334-337.
[11]韦长元,黎丹戎,曹骥等.板蓝根组酸诱导耐药人肝癌原位移植瘤的细胞凋亡研究.广西医学.2004,26(5):640-642.
[12]秦箐,贺海平,Soren Brogger Christensen等.中药板蓝根中蓝色流分的分离及其对体外人多形核细胞化学发光的影响.广西医科大学学报,2001,18(2):196-197.
[13]秦箐,贺海平,Soren Brogger Christensen等.中药板蓝根两个高极性流分的分离及其活性的研究.中国药理学通报,2001,17(6):714-715.
[14]秦箐,侯华新,邱莉等.板蓝根高极性流分及其亚流分抗氧自由基的活性.中国临床药学杂志,2001,10(6):373-375.
[15]侯华新,秦箐,黎丹戎等.板蓝根高级不饱和脂肪组酸的体外抗人肝癌BEL-7402细胞活性.中国临床药学杂志,2002,11(1):16-19.
[16]刘家仁,陈炳卿,邓皓.共轭亚油酸诱导人胃腺癌细胞(SGC-7901)凋亡作用.工业卫生与职业病,2001,27(3):129-132.
[17]杨艳梅,等.共轭亚油酸对人胃腺癌细胞侵袭及转移相关基因表达的影响.中华预防医学杂志,2003,37(1):26-28.
[18] Beck SA,Smith KL,Tisdale MJ.Anticacbectic and antitumor effect 0f eicosapentaenoic acid its effect on protein turnover [J].Cancer Res,1991,51(22):6089-6093.
[19]Wallace FA,Neely SJ,Miles EA,eta1.Dietary fats affect macrophage-mediated cytotoxicity towards tumour cells [J].Immunol Cell Biol,2000,78(1):40-48.
[20]尹勇,詹文华,彭俊生,赵宗刚.ω-3多不饱和脂肪酸诱导人胃癌.中华胃肠外科杂志.2007, l0(6) :570-573.
[21] Ran ZH,Xu Q,Tong JL,et a1. Apoptofic efect of Epigallocatechin-3-gallate on the human gastric cancer cell line MKN45 via activation of the mitochondrial pathway [J]. W0rld J Gastroenterol,2007,13:425—4259.
[22] Robert S, Chapkin,etal.Dietary n?3PUFA alter colonocyte mitochondrial membrane composition and function [J].Lipids,2002 2(37) :193-199.
[23] Danbara N, Yuri T, Tsujita2KyutokuM, etal. Conjugated docosahexaenoic acid is a potent inducer of cell cycle arrest and apop tosis and inhibits growth of colo 201 human colon cancer cells [J].Nutr Cancer, 2004, 50 (1) : 71-79.
[24] HardmanWE. ( n-3) fatty acids and cancer therapy [J]. J Nutr,2004, 134 (12 Supp l) : 3427S-3430S.
[25] Iioka Y, Mishima K, Azuma N, eta1. Overexpression of Protein Kinase C Enhances Cisplatin-Induced Cytotoxicity Correlated with p53 in Gastric Cancer Cell Line [J]. Pathobiology.2005,72(3):152—159.
[26] Okumura S,Baba H,Kumada T,eta1.Cloning of aG-protein—coupled receptor that shows an activity to transform NIH3T3 cells and is expressed in gastric cancer cells [J]. Cancer Sci.2004,95(2):131- 135.
[27] Kato T, Hancock RL, eta1. Influence of omega-3 fatty acids on the growth of human colon carcinoma in nude mice [J]. Cancer lett .2002 ,187(1-2):169-177.
[28] M Takahashi , M Przetakiewicz , A Ong , etal. Effect ofω-3 andω-6 fatty acids on transformation of cultured cells by irradiation and transfection [J]. Cancer Res .1992 , 52 ( 1) :154-162.
[29] YP Zhu , ZW Su , CH Li. Growth-inhibition effects of oleic acid , linoleic acid , and their methy1 esters on transplanted tumors in mice [J]. Nat1 Cancer Inst.1989 , 81 ( 17 ) :1302 -1306.
[30] DB Charles , MA Lea. Effects of C18 fatty acid isomers on DNA synthesis in hepatoma and breast cancer cells [J]. Anti-cancer Res .1995 , 15 (5B) : 2017-2021.
[31]郭诗玖,董成代,刘邦玲等.油酸多相脂质体(PL139)对恶性肿瘤疗效观察.肿瘤.1989,9(1):35.
[32]孙润广,张静,王永昌.脂肪酸多相脂质体与癌细胞膜相互作用的ESR谱研究.生物化学与生物物理进展. 200,27(3):296-300
[33]陈爱军,朱耀明,杨振华.DHA在人乳腺癌中对阿霉素活性的影响与脂质过氧化作用的关系.中国肿瘤临床与康复,2002,9(4):22-29.
[34] Das U. A radical approach to cancer [J].Med Sci Monit. 2002,8:79-92.
[35] Thompson H, Zhu Z, Banni S, et al. Morphological and Biochemical status and the mammary gland as influenced by conjugated linoleic acid: implycation for a reduction in mammary cancer risk [J]. cancer Res. 1997,57(22): 5067-5072.
[36] Cesano A, Visonneau S, Scimeca JA, etal. Opposite effects of linoleic acid and congated linoleic acid on human prostatic cancer in SCID mice [J]. Anticancer Res.1998,18(3A): 1429-1434.
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