用户名: 密码: 验证码:
参芪扶正注射液对化疗增效作用的分子机制研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
1目的
     探讨参芪扶正注射液对化疗干预下小鼠肝转移癌组织基因表达谱的影响
     2方法
     2.1构建结肠癌肝转移小鼠模型
     选用BALB/c小鼠,将传代三次后的小鼠结肠癌C26瘤细胞液脾内注射后切除脾脏,建立实验模型。
     2.2分组给药
     造模小鼠共20只,分为两组,每组10只。5-氟尿嘧啶组(5-Fu组);5-氟尿嘧啶+参芪扶正注射液组(5-Fu+参芪组)。
     2.3观察指标
     接种瘤株后每日称重,观察其活动、饮食及肿瘤发展情况。造模后第12天处死荷瘤小鼠,将肝转移癌组织取出称重后迅速液氮冻存备用。进行样品核酸制备、基因芯片检测及差异基因筛选,将筛选后的差异基因数据录入博奥生物有限公司分子功能注释系统进行生物信息学分析,解释药物的作用机理。
     3结果
     3.1造模成功率100%;
     3.2基因表达分析
     参芪扶正注射液可显著下调基因282个;上调基因13个。
     4结论
     参芪扶正注射液可能通过显著影响恶性肿瘤的多条信号转导通路,包括氧化磷酸化、嘌呤及嘧啶代谢、血管内皮生长因子信号转导通路、黏着连接、黏着斑等,实现对化疗的增效作用。
1 Objective
     To explore effects of ShenQiFuZheng injection on gene expression profile of liver metastasis cancer in mice suffering chemotherapy.
     2 Methods
     2.1 Constructing mouse model of liver metastasis cancer
     Selecting BALB/c mice, establish the experimental models by cutting spleens after injecting C26 mouse colon cancer cells in them.
     2.2 Group and Administration
     20 Mouse models of liver metastasis cancer were set up and then randomly divided into two groups:5-Fu group, Shenqi Fuzheng Injection+5-Fu group.
     2.3 Observation
     Mice were weighted every day after being inoculated tumor cells. Observe the activity, appetite and the development of tumors. Tumor-bearing mouse were sacrificed at the thirteenth day. Tumor tissues were weighed and reserved with liquid nitrogen, then prepare the nucleic acid, detect the gene chips and analyse the genes with bioinformatics.
     3 Results
     3.1 All mouse models were set up sucessfully;
     3.2 Gene expression
     ShenQiFuZheng injection could up-regulate 13 genes and down-regulate 282 genes.
     4 Conclusions
     ShenQiFuZheng Injection can affect Several signal pathways in the tumor, including oxidative phosphorylation, purine metabolism, pyrimidine metabolism, VEGF signaling pathway, adherens junction, focal adhesion.
引文
[1]刘嘉湘.阴阳平衡与扶正治癌理论在癌症治疗中的应用.江苏中医药,2008,40(9):1.
    [2]何任.论补法.浙江中医药大学学报,2008,32(3):315.
    [3]华海清.扶正培本法治疗恶性肿瘤探讨.南京中医药大学学报,2008,24(1):6-8.
    [4]吕立国,古炽明,王昭辉,等.陈志强教授对晚期前列腺癌中医病因病机的探讨.新中医,2007,39(2):81-82.
    [5]赵映前.试论前列腺癌的中医学研究思路与方法.中医药研究,2000,16(3):2.
    [6]吕立国,陈志强,王树声,等.中西医结合扶正抑瘤法治疗前列腺癌142例临床观察.新中医,2008,40(1):26-27.
    [7]张亚强,林飞.前列消瘢汤治疗前列腺癌的临床观察.中国中西医结合外科杂志,2006,12(2):83.
    [8]潘明继.癌症扶正培本治疗学.第1版.上海:复旦大学出版社,2003:301.
    [9]张莉,张仲海,徐勤,等.扶正消瘤汤对乳腺癌患者生存质量及免疫功能影响临床研究.实用中医药杂志,2008,24(8):482-483.
    [10]姚志华,张明智.中药抗恶性肿瘤研究进展.现代肿瘤医学,2006,14(4):503-505.
    [11]朱琨,李康,党诚学.参芪扶正注射液对乳腺癌术后行CEF方案化疗患者免疫功能的影响.现代肿瘤医学,2008,16(10):1712-1714.
    [12]杨波,李洪胜,祁岩超,等.扶正培本法配合化疗治疗乳腺癌的临床研究.中药材,2007,30(12):1629-1631.
    [13]王敏,安祯祥.中晚期胃癌中西医结合治疗的临证思路探析.辽宁中医杂志,2008,35(3):379-380.
    [14]宋恩峰,张新.孙桂芝防治胃癌复发转移的经验.湖北中医杂志,1995,17(6):4-5.
    [15]宋家驹.健脾中药抗胃癌术后转移的研究.现代中西医杂志,2004,13(22):2956.
    [16]陈建华,王琪雁.扶正抗癌冲剂对中晚期胃癌免疫治疗作用的研究.辽宁中医杂志,2008,35(5):717-718.
    [17]陈曦.扶正消瘤汤治疗中晚期胃癌46例临床观察.航空航天医药,2008,19(2):99.
    [18]李素领.运用中医药治疗原发性肝癌的体会.中医研究,2008,21(12):44.
    [19]陆运鑫,黄丁平,侯恩存,等.康艾注射液联合肝动脉栓塞化疗治疗原发性肝癌的临床疗效观察.中国中药杂志,2007,32(24):2655-2656.
    [20]刘娇林,王晓林,郭晓光,等.化疗伍用扶正抑癌方治疗中晚期肝癌33例.中医研究,2005,18(4):34-36.
    [21]余桂芳,曾文铤,朱科伦,等.三氧化二砷与人参皂甙Rg3联合对于肝癌SMMC7721细胞侵袭转移能力的影响.疑难病杂志,2007,6(1):23-26.
    [22]American Cancer Society. Cancerfactsandfigueres 2006. Atlanta:American Cancer Society,2006:13-14.
    [23]刘海涛,戴锡孟.中药扶正合剂对L795肺癌小鼠作用的观察.辽宁中医杂志,2004,31(3):254-255.
    [24]王兆会,谭军华,刘鸿.扶正防毒汤对肺癌化疗减毒作用的观察.安徽中医学院学报,2006,25(3):16.
    [25]刘嘉湘,等.金复康口服液治疗原发性非小细胞肺癌临床研究。肿瘤,2001,21(6):463.
    [26]赵远红,李正.扶正降逆法在肿瘤化疗期消化道反应中的应用研究.新中医,2008,40(1):30-31.
    [27]刘征雁,宋振民,刘丰,等.九味养血片合参麦注射液减轻化疗毒副作用的临床观察.光明中医,2004,19(1):58-59.
    [28]赵小青,裴晓峰,张爽.中药扶正在化疗过程中时间强度密度的应用探讨.辽宁中医杂志,2008,35(4):521-522.
    [29]罗政,邹凌云,万会平.扶正消瘕法在大肠癌术后化疗期间调节免疫功能的临床与实验研究.世界肿瘤杂志,2008,7(1),16-23.
    [1]丁治国,李乃卿,陶德胜,刘东来,杨扬,史晓光,邢光明,魏永煜,李兰芳.参芪扶正注射液对小鼠肝转移癌组织基因表达谱的影响[J].中国中西医结合杂志,2008,28(2):135-138.
    [2]施丽飞,薛大方,李红,孙卫民,滕文锋.ICP-MS分析参芪扶正注射液中14种微量元素的含量[J].药学实践杂志,2008,26(1):41-42.
    [3]杨克敌.微量元素与健康[M].北京:科学出版社,2003,85,94.
    [4]朱小玉,陈运贤,钟雪云,张祥忠,刘建华,何敏.参芪扶正注射液对化疗后小鼠免疫功能的保护作用研究[J].中国免疫学,2006,22(10):925-926.
    [5]梅宏,陈志昌.参芪扶正注射液对肺癌患者手术后免疫功能的调节作用[J].四川大学学报(医学版),2005,35(3):449.
    [6]袁建伟,孔长保,康国庆,刘行凤,杨诗杰.参芪扶正注射液对乳腺癌新辅助化疗患者细胞免疫功能的影响[J].时珍国医国药,2008,19(5):1099-1100.
    [7]张彦表,胥欣,韩成冰,韩婷婷,曹雪梅.参芪扶正注射液对RAU大鼠外周血T细胞亚群的影响[J].中国医药导报,2008,5(16):34-35.
    [8]宋岚,徐朝军,黄春林,张彩平,乔新惠.参芪扶正注射液对肺癌小鼠顺铂化疗后免疫功能的影响[J].实用全科医学,2008,9(4):1-2.
    [9]王晓稼,王晓婷,金琪琪.参芪扶正注射液对多柔比星致家兔心肌和免疫功能损伤的保护作用[J].实用肿瘤杂志,2005,20(4):314.
    [10]狄 灵,杨成志,刘素蓉.参芪扶正注射液对小鼠心肌缺血再灌注损伤诱发心肌细胞凋亡的保护作用初探[J].实用中医药学杂志,2005,21(2):67.
    [11]陆 雷,潘轶斌,张怀勤.参芪扶正注射液治疗冠心病心衰的疗效观察[J].心脑血管病防治,2005,5(3):33-34.
    [12]李中和,刘章锁,侯秀芳,等.口服参芪扶正注射液对糖尿病大鼠肾脏的保护作用[J].中国医院药学杂志,2002,22(1):15.
    [13]吴 歌,张有才,刘章锁,等.参芪扶正注射液对糖尿病大鼠肾脏的保护作用[J].河南医科大学学报,2000,36(6):540.
    [14]宁亚利,姚淑莲,李东辉,郭卉,李珉,陈星.参芪扶正注射液对表阿霉素心脏毒性保护作用的临床研究[J].陕西中医,2008,29(2):159-161.
    [15]任 映,谢伟宏,宋崇顺,等.参芪扶正注射液与临床常用抗肿瘤药相配伍的实验研究[J].中华中西医临床杂志,2004,4(1):43.
    [16]钟陆行,熊建萍,张锡泉,参芪扶正注射液对K562/ADM多药耐药的影响[J].江西医学院学报2006,46(4):41-43.
    [17]李宁,杨卫兵.参芪扶正注射液配合化疗治疗中晚期恶性肿瘤疗效观察[J].四川中医2005,23(7):44-45.
    [18]柏长青,宋颖芳,王德堂,郭惠玲.黄芪、党参提取物抑制肺癌细胞诱导血管内皮细胞迁移的实验研究[J].武警医学,2008,19(6):505-508.
    [19]蒋莹,庄文斌,周宁,参芪扶正注射液配合化疗治疗晚期肺癌的疗效观察[J].中国药房.2005,16(10):772.
    [20]潘彦康,黄敏,区梅.参芪扶正注射液辅助化疗治疗非小细胞肺癌临床观察[J].中国临床医生.2008,36(4):43.
    [21]何文杰,赵金奇.参芪扶正注射液联合吉西他滨加顺铂方案治疗晚期非小细胞肺癌的临床观察[J].医学综述.2008,36(4):43-45.
    [22]杨明会,窦永起,刘哲峰.活血化痕药物防治放射性肺损伤的实验研究[J].中国中西医结合杂志2005;25(12):1096-1099.
    [23]焦红军.党参的药理作用及其临床应用[J].临床医学2005;25(14):92.
    [24]RobcCE, WifertF, UtheD, etal. Modulation of irradiation-indueed tumor neerosis faetor(TNF-a) expression in the lung tissue by Pentoxifyline.Int J Radiat neol Biol Phys, 2003;56(6):1414-1425.
    [25]成慧君,朱霞,葛红.参芪注射液配合化疗治疗消化道肿瘤[J].医药论坛.2006,15(27),40.
    [26]李兆元,黄秋华,徐海声,阮晓峰.参芪扶正注射液联合化疗治疗胃癌疗效观察.辽宁中医药大学学报2006,8(6):89.
    [27]姜志平,陈方平.参芪扶正注射液联合VAD方案治疗多发性骨髓瘤临床研究[J].现代肿瘤医学,2008,16(2):298.
    [28]陈芳,林红.参芪扶正注射液辅助乳癌化疗的疗效观察[J].海峡药学,2007,19(12):75-76.
    [29]黄智芬,韦劲松,黎汉忠,谭志强,张作军,陈 闯.参芪扶正注射液联合化疗治疗晚期乳腺癌30例临床观察.[J].中国中西医结合杂志2008,28(2):152-153.
    [30]任渐平,李先明,吴超权,胡岳然,陈善义,刘雅洁.参芪扶正注射液对乳腺癌术后放疗保护作用的临床观察.中医药学报2005,33(3):32-33.
    [31]孙素红,郑兴斌.参芪扶正注射液在乳癌术后化疗中的应用.[J].中国中西医结合杂志2005,25(6):544-545.
    [32]周光新,吴苏稼,施鑫,陆萌,黎承军.参芪扶正注射液在骨肉瘤化疗中的临床应用.[J].中国医刊2007,42(12):62.
    [33]赵刚.参芪扶正注射液在脑转移瘤化疗中辅助作用的疗效观察.[J].中国医院药学杂志2008,28(1):49-51.
    [34]国家中医药管理局冲药现代研究与临床应用[M].北京:人民卫生出版社,1995.
    [35]辛明,全金华,周春宁,等.参芪扶正注射液配合化疗治疗消化道恶性肿瘤的临床观察[J].中国中西医结合杂志,1998,18(11):103-107.
    [1]刘嘉湘.阴阳平衡与扶正治癌理论在癌症治疗中的应用.江苏中医药,2008,40(9):1-2.
    [2]丁治国,史晓光,李兰芳等.流式微球技术检测参芪扶正注射液对化疗小鼠Th1/Th2平衡状态的影响[J].中国实验方剂学杂志.2009.15(5):39-41.
    [3]李宁,杨卫兵.参芪扶正注射液配合化疗治疗中晚期恶性肿瘤疗效观察[J].四川中医.2005.23(7):44-45.
    [4]姜桂林.参芪扶正注射液对恶性肿瘤患者辅助化疗的疗效观察[J].河北中医.2005.27(9):701-702.
    [5]孙呈祥,李春燕,孙宝兰.参芪扶正注射液辅助化疗治疗晚期恶性肿瘤48例[J].中西医结合学报.2004.2(4):270+305.
    [6]邹彦,柏玉举等.参芪扶正注射液联合紫杉醇加卡铂治疗晚期非小细胞肺癌临床观察[J].实用肿瘤杂志.2005.20(3):260-262.
    [7]Zhong H, De Marzo AM, Laughner E, et al. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases[J]. Cancer Res,1999,59(22):5830-5835.
    [8]Carmelie P, Jain RK. Angiogenesis in cancer and other diseases[J]. Nature,2000, 407(6801):249-257.
    [9]Hewett PW, Murray JC. Coexpression of flt-1, flt-4 and KDR in freshly isolated and cultured human endothelial cells[J]. Biochem Biophys Res Commun,1996,221(3):697-702.
    [10]He Y, Kozaki K, Karpanen T, Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling[J]. J Natl Cancer Inst,2002,94(11):819-825.
    [11]Akira S, Takeda K. Toll-like receptor signalling[J]. Nat Rev Immunol,2004,4(7): 499-511.
    [12]Kopp E, Medzhitov R. Recognition of microbial infection by Toll-like receptors[J]. Curr Opin Immunol.,2003,15(4):396-401.
    [13]Ockaili R, Natarajan R, Salloum F, et al. HIF-1 activation attenuates postischemic myocardial injury:role for heme oxygenase-1 in modulating microvascular chemokine generation[J]. Am J Physiol Heart Circ Physiol,2005,289(2):542-548.
    [14]Lee YJ, Swencki B, Shoichet S, et al. A possible role for the high mobility group box transcription factor Tcf-4 in vertebrate gut epithelial cell differentiation. [J]. J Biol Chem, 1999,274(3):1566-1572.
    [15]Korinek V, Barker N, Morin PJ, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/-colon carcinoma [J]. Science,1997,275(5307): 1784-1787.
    [16]Fasolini M, Wu X, Flocco M, et al. Hot spots in Tcf4 for the interaction with beta-catenin. [J]. J Biol Chem,2003,278(23):21092-21098.
    [17]Noritake J, Watanabe T, Sato K, et al. IQGAP1:a key regulator of adhesion and migration [J]. J Cell Sci,2005,118(10):2085-2092.
    [18]Brown MD, Sacks DB. IQGAP1 in cellular signaling:bridging the GAP [J]. Trends Cell Biol,2006,16(5):242-249.
    [19]Watanabe T, Wang S, Noritake J, et al. Interaction with IQGAP1 links APC to Racl, Cdc42 and actin filaments during cell polarization and migration [J]. Dev Cell,2004,7(6): 871-883.
    [20]Yamaoka-Tojo M, Ushio-Fukai M, Hilenski L, et al. IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species-dependent endothelial migration and proliferation[J]. Circ Res,2004,95(3): 276-283.
    [21]Zhao ZS, Manser E. PAK and other Rho-associated kinases-effectors with surprisingly diverse mechanisms of regulation[J]. Biochem J,2005,386(Pt 2):201-214.
    [22]Eswaran J, Lee WH, Debreczeni JE, et al. Crystal Structures of the p21-activated kinases PAK4, PAK5 and PAK6 reveal catalytic domain plasticity of active group II PAKs[J]. Structure,2007,15(2):201-213.
    [23]Mahlamaki EH, Kauraniemi P, Monni O, et al. High-resolution genomic and expression profiling reveals 105 putative amplification target genes in pancreatic cancer[J]. Neoplasia, 2004,6(5):432-439.
    [24]秦军,陈宝琦,刘佃成.血小板衍生生长因子受体在膀胱癌中的表达意义[J].第四军医大学学报,2001,22(8):714-717.
    [25]李哲夫,陈孝平,张万广.肝细胞癌合并门静脉癌栓组织中PDGF和survivin表达的意义[J].中国普外基础与临床杂志,2007,14(1):307-308.
    [26]Stacker SA, Caesar C, Baldwin ME, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics [J]. Nat Med,2001,7(2):186-191.
    [27]Veikkola T, Jussila L, Makinen T, et al. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice [J]. EMBOJ,2001,20(6): 1223-1231.
    [28]Goepel C, Stoerer S, Koelbl H. Tenascin in preinvasive lesions of the vulva and vulvar cancer [J]. Anticancer Res.2003,23(6):4587-4591.
    [29]Brunner A, Mayerl C, Tzankov A, et al. Prognostic significance of tenascin-C expression in superficial and invasive bladder cancer [J]. J Clin Pathol,2004,57(9):927-931.
    [30]Chiquet-Ehrismann R. Tenascin and other adhesion-modulating proteins in cancer [J]. Semin Cancer Biol,1993,4(5):301-310.
    [31]Yoshida T, Ishihara A, Hirokawa Y, et al. Tenascin in breast cancer development-is epithelial tenascin a marker for poor prognosis? [J]. Cancer Lett,1995,90(1):65-73.
    [32]Tok e s AM, Paku S, Toth S, et al. Tenascin expression in primary and recurrent breast carcinomas and the effect of tenascin on breast tumor cell cultures [J]. Pathol Oncol Res, 2000,6(3):202-209.
    [33]Kadar A, Tokes AM, Kulka J, et al. Extracellular matrix components in breast carcinomas [J]. Semin Cancer Biol,2002,12(3):243-257.
    [34]Jahkola T, Toivonen T, von Smitten K, et al. Expression of tenascin in invasion border of early breast cancer correlates with higher risk of distant metastasis [J]. Int J Cancer.1996, 69(6):445-447.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700