来自加拿大皇后大学（Queen's University）生物化学系，多伦多大学，以及美国Palo Alto卫生保健系统（Palo Alto Health Care System），印第安纳州医学院（Indiana University School of Medicine）等处的研究人员在实验室研究一种多肽分子（ANK）与抗乳腺癌药物合用药效的时候，意外发现这种分子大大增强了药力，从而希望能通过进一步研究，配合传统抗乳腺癌药物进行分子疗法，给有抗药性的乳腺癌病人使用，加强药物药效。这一研究成果公布在1月15日的《Cancer Research》杂志上。
领导这一研究的是加拿大皇后大学的贾宗超(Zongchao Jia)教授。
乳腺癌主要发生于女性，是危害妇女健康的主要恶性肿瘤，仅次于宫颈癌，在女性恶性肿瘤发病率中居第2位。全世界每年约有120万妇女发现乳腺癌，有50万妇女死于乳腺癌。北美、北欧是乳腺癌的高发地区，其发病率约为亚、非、拉美地区的4倍。我国是乳腺癌的低发地区，但其发病率正逐年上升，尤其沪、京、津等大城市及沿海地区。
在对乳腺癌患者（advanced or metastatic diseases）的治疗过程中，经常会使用抗微小管（Antimicrotubule）药物，但是病患对这种典型化疗的反应变化极大，不稳定。
在这篇文章中，研究人员设计了一种新颖的多肽ANK，并利用一些生物学方法（荧光计，表面等离子共振技术（surface plasmon resonance），等温滴定量热法（isothermal titration calorimetry））证明了ANK与SNGG之间的关系。
Synuclein-γ (SNCG)，又称为BCSG1 (breast cancer specific gene 1)或persyn，属于synuclein家庭成员，这类蛋白是一个广泛分布于中枢神经系统突触前成分内的小分子蛋白质家族，有α-synuclein、β-synuclein和γ-synuclein三个成员，其中SNGG被发现与乳腺癌细胞的生长、浸润、转移和预后有关。
研究人员将ANK缩氨酸与标准药物合并，放入装有乳癌细胞的培养皿中进行效力测试，他们也单独使用药物测试。结果发现，添加缩氨酸的药物比不加缩氨酸药物杀死的癌细胞多3.5倍。
这说明这种缩氨酸可以促进目前最广泛应用乳腺癌药物的功效，这对于那些有严重抗药问题的患者意义重大。
不过研究人员也指出现在只是研究早期阶段，结果只限于实验室实验，下一步会在实验室老鼠身上实验。如果成功，他们会进入人体测试，这个过程可能需时几年。这一缩氨酸已申请了一项美国专利。
附：
贾宗超，北京师范大学长江学者讲座教授。
生物化学。博士生导师。
贾宗超，北京师范大学教授，2004年受聘为国家教育部“长江学者奖励计划讲座教授”，聘任岗位：生物化学。
部分英文原文：
Experimental Therapeutics, Molecular Targets, and Chemical Biology
Synuclein- Targeting Peptide Inhibitor that Enhances Sensitivity of Breast Cancer Cells to Antimicrotubule Drugs
Vinay K. Singh1, Yue Zhou2, Joseph A. Marsh3,4, Vladimir N. Uversky5, Julie D. Forman-Kay3,4, Jingwen Liu2 and Zongchao Jia1
1 Department of Biochemistry, Queen's University, Kingston, Ontario, Canada; 2 Department of Veterans Affairs, Palo Alto Health Care System, Palo Alto, California; 3 Molecular Structure and Function, Hospital for Sick Children; 4 Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada; and 5 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana
Requests for reprints: Zongchao Jia, Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6. Phone: 613-533-6277; Fax: 613-533-2497; E-mail: jia@post.queensu.ca or Jingwen Liu, Department of Veterans Affairs, Palo Alto, CA 94304. Phone: 650-493-5000, ext. 64411; Fax: 650-849-0251; E-mail: Jingwen.Liu@med.va.gov .
Synuclein- (SNCG) plays oncogenic roles in breast carcinogenesis. Although the expression of SNCG is abnormally high in advanced and metastatic breast carcinomas, SNCG is not expressed in normal or benign breast tissues. SNCG is an intrinsically disordered protein known to interact with BubR1, a mitotic checkpoint kinase. The SNCG-BubR1 interaction inhibits mitotic checkpoint control upon spindle damage caused by anticancer drugs, such as nocodazole and taxol. Antimicrotubule drugs that cause mitotic arrest and subsequent apoptosis of cancer cells are frequently used to treat breast cancer patients with advanced or metastatic diseases. However, patient response rates to this class of chemotherapeutic agents vary significantly. In this study, we have designed a novel peptide (ANK) and shown its interaction with SNCG using fluorometry, surface plasmon resonance, and isothermal titration calorimetry. Binding of the ANK peptide did not induce folding of SNCG, suggesting that SNCG can function biologically in its intrinsically disordered state. Microinjection of the ANK peptide in breast cancer cell line overexpressing SNCG (MCF7-SNCG) exhibited a similar cell killing response by nocodazole as in the SNCG-negative MCF7 cells. Overexpression of enhanced green fluorescent protein–tagged ANK reduces SNCG-mediated resistance to paclitaxel treatment by 3.5-fold. Our coimmunoprecipitation and colocalization results confirmed the intracellular association of the ANK peptide with SNCG. This is likely due to the disruption of the interaction of SNCG with BubR1 interaction. Our findings shed light on the molecular mechanism of the ANK peptide in releasing SNCG-mediated drug resistance. [Cancer Res 2007;67(2):626–33]
更多乳腺癌文献资料...
http://cancerres.aacrjournals.org/cgi/content/abstract/67/2/626
