王宏;孙治君;钟彪;

• 1:重庆医科大学附属第二医院普外科

摘要(Abstract)：

目的探讨乌司他丁(Ulinastatin,UTI)和泰索帝(Taxotere,TXT)对人原代乳腺癌细胞增殖、侵袭及胰岛素样生长因子受体1(Insulin-like growth factor 1 receptor,IGF-1R)、血小板衍生因子A(Platelet-derived growth factor A,PDGFA)和血小板活化因子受体(Platelet-activating factor receptor,PAFR)表达的影响。方法将原代培养的乳腺癌细胞分为4组:UTI组(800 IU/ml)、TXT组(3.7μg/ml)、UTI+TXT组和培养液对照组,MTT法检测细胞的增殖活力;Transwell小室法检测细胞的侵袭能力;流式细胞仪检测细胞凋亡情况;RT-PCR和Western blot检测细胞中IGF-1R、PDGFA及PAFR基因mRNA的转录水平及蛋白的表达水平。结果 UTI和TXT均可显著抑制人原代乳腺癌细胞的增殖和侵袭能力,诱导细胞凋亡,下调细胞中IGF-1R、PDGFA及PAFR基因mRNA的转录水平和蛋白的表达水平,且UTI与TXT联合使用时效果更为明显。结论 UTI能够增强TXT对人原代乳腺癌细胞的抑制作用,二者具有协同效应,这种机制可能与UTI影响IGF-1R、PDGFA和PAFR的表达有关。

关键词(KeyWords)： 乌司他丁;泰索帝;乳腺肿瘤;受体,IGF-1型;血小板衍生因子A;血小板活化因子受体

Abstract:

Keywords:

基金项目(Foundation): 重庆市科技攻关项目(CSTC,2008AC5082)

作者(Author): 王宏;孙治君;钟彪;

Email:

DOI: 10.13200/j.cjb.2012.01.77.wangh.024

参考文献(References)：

• [1]吴在德,吴肇汉.外科学[M].6版.北京:人民卫生出版社,2004:321-332.
• [2]钟彪,孙治君,付裕,等.乌司他丁和泰索帝对人原代乳腺癌细胞增殖、侵袭、凋亡的影响及其机制[J].中国生物制品学杂志,2011,24(10):1197-1202.
• [3]Van Der Kuip H,Mürdter TE,Sonnenberg M,et al.Short termculture of breast cancer tissues to study the activity of the anti-cancer drug taxol in an intact tumor environment[J].BMC Can-cer,2006,6:86-96.中国生物制品学杂志2012年1月第25卷第1期Chin J Biologicals January2012,Vol.25No.1
• [4]Kobayashi H,Shinohara H,Takeuchi K,et al.Inhibition of thesoluble and the tumor cell receptor-bound plasmin by urinarytrypsin inhibitor and subsequent effects on tumor cell invasion andmetastasis[J].Cancer Res,1994,54(3):844-849.
• [5]魏爱英,马春燕,牟文丽.多烯紫杉醇抑制乳腺肿瘤细胞增殖及诱导凋亡的实验研究[J].山东医药,2005,45(8):22-23.
• [6]Koechli OR,Avner BP,Sevin BU.Application of the adenosinetriphosphate-cell viability assay in human breast cancer chemosen-sitivity testing:a report on the first results[J].J Surg Oncol,2003,54(2):119-125.
• [7]Pugia MJ,Lott JA.Pathophysiology and diagnostic value of urinarytrypsin inhibitors[J].Clin Chem Lab Med,2005,43(1):1-16.
• [8]Kobayashi H,Shinohara H,Gotoh J,et al.Anti-metastatic thera-py by urinary trypsin inhibitor in combination with an anti-canceragent[J].Br J Cancer,1995,72(5):1131-1137.
• [9]Sachdev D,Zhang X,Matise I,et al.The type I insulin-likegrowth factor receptor regulates cancer metastasis independently ofprimary tumor growth by promoting invasion and survival[J].Oncogene,2010,29(2):251-262.
• [10]Yanochko GM,Eckhart W.Type I insulin-like growth factor re-ceptor over-expression induces proliferation and anti-apoptoticsignaling in a three-dimensional culture model of breast epithelialcells[J].Breast Cancer Res,2006,8(2):R18.
• [11]Shen MR,Hsu YM,Hsu KF,et al.Insulin-like growth factor 1is a potent stimulator of cervical cancer cell invasiveness and pro-liferation that is modulated byαvβ3 integrin signaling[J].Car-cinogenesis,2006,27(5):962-971.
• [12]Zeng X,Sachdev D,Zhang H,et al.Sequencing of type I in-sulin-like growth factor receptor(IGFIR)inhibition affects chem-otherapy response in vitro and in vivo[J].Clin Cancer Res,2009,15(8):2840-2849.
• [13]Jechlinger M,Sommer A,Moriggl R,et al.Autocrine PDGFRsignaling promotes mammary cancer metastasis[J].J Clin Invest,2006,116(6):1561-1570.
• [14]Carvalho I,Milanezi F,Martins A,et al.Overexpression ofplatelet-derived growth factor receptorαin breast cancer is asso-ciated with tumour progression[J].Breast Cancer Res,2005,7(5):P788-P795.
• [15]Pasanisi P,Venturelli E,Morelli D,et al.Serum insulin-likegrowth factor-i and platelet-derived growth factor as biomarkers ofbreast cancer prognosis[J].Cancer epidemiol biomarkers Prev,2008,17(7):1719-1722.
• [16]Lev DC,Kim SJ,Onn A,et al.Inhibition of platelet-derivedgrowth factor receptor signaling restricts the growth of humanbreast cancer in the bone of nude mice[J].Clin Cancer Res,2005,11(1):306-314.
• [17]Kang DW,Min do S.Platelet derived growth factor increasesphospholipase D1 but not phospholipase D2 expression viaNFkappaB signaling pathway and enhances invasion of breastcancer cells[J].Cancer Lett,2010,294(1):125-133.
• [18]Melnikova VO,Balasubramanian K,Villares GJ,et al.Crosstalkbetween protease-activated receptor 1 and platelet-activating fac-tor receptor regulates melanoma cell adhesion molecule(MCAM/MUC18)expression and melanoma metastasis[J].J Biol Chem,2009,284(42):28845-28855.
• [19]Aponte M,Jiang W,Lakkis M,et al.Activation of platelet-acti-vating factor-receptor and pleiotropic effects on tyrosine phospho-EGFR/Src/FAK/Paxillin in ovarian cancer[J].Cancer Res,2008,68(14):5839–5848.
• [20]Melnikova VO,Mourad-Zeidan AA,Lev DC,et al.Platelet-acti-vating factor mediates MMP-2 expression and activation via phos-phorylation of cAMP-response element-binding protein and con-tributes to melanoma metastasis[J].J Biol Chem,2006,281(5):2911-2922.
• [21]De Oliveira SI,Andrade LN,Onuchic AC,et al.Platelet-acti-vating factor receptor(PAF-R)-dependent pathways control tu-mour growth and tumour response to chemotherapy[J].BMCCancer,2010,10:200-211.
• [22]Cellai C,Laurenzana A,Vannucchi AM,et al.Growth inhibi-tion and differentiation of human breast cancer cells by the PAFRantagonist WEB-2086[J].Br J Cancer,2006,94(11):1637-1642.