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肿瘤预防与治疗研究
发布人:高雪  发布时间:2014-12-17  

 

研究室概况

      本研究室主要致力于传统中药抗肿瘤作用及其作用机理的研究。蛋白酶体为抗癌药物作用的分子靶点之一,我们通过计算机模拟技术对蛋白酶体靶向性中药成分进行预测,并结合体内外实验探讨其在肿瘤预防与治疗上的潜在应用,及其对临床应用的化疗药物的增敏作用。此外,鉴于自噬是肿瘤细胞对蛋白酶体抑制剂耐受的原因之一,本研究室也关注蛋白酶体抑制剂诱导的细胞自噬的调控机制,包括转录因子及miRNA对细胞自噬的调控。

人才培养

研究室教师面向本科生、硕士研究生和博士研究生承担生物化学、细胞生物学、分子生物学创新实验等各类课程的教学任务,并欢迎各类学生进入实验室进行创新研究。研究室在生物学学科招收细胞生物学,生化与分子生物学方向的理学硕士;在生物医学工程学科招收肿瘤分子细胞生物学理学博士和博士后。

主要研究方向

1. 天然抗肿瘤药物的筛选与机理研究

恶性肿瘤是目前危害人类健康的主要疾病之一。寻找有效的抗肿瘤药物是肿瘤研究中的关注的重点。本研究室从传统中药出发,利用计算机模拟筛选靶向蛋白酶体的抗肿瘤药,并在体内、体外研究其抗癌作用机制。

2. 肿瘤细胞自噬调控机制

多种肿瘤的发生、发展、侵袭及转移过程中均发现自噬活动的异常。本研究室通过microarray、体内、体外实验分析相关基因表达情况及相关信号通路的响应情况,研究肿瘤细胞中的自噬调节机制,并进一步探索自噬与肿瘤细胞凋亡的联系。

3. 肿瘤细胞化疗增敏   

化疗是癌症治疗的有效手段之一,但化疗药物在杀伤肿瘤细胞的同时,也对人体产生了不同程度的毒副作用。本研究室探索天然药物作为化疗增敏剂,以增加肿瘤细胞对化疗的敏感性,减轻化疗的毒副反应。并研究天然药物作为化疗增敏剂的作用机制。

4. 上皮间充质转化

EMT 是指上皮细胞在特定的生理和病理情况下向间质细胞转化的现象。近年来人们日益认识到EMT与肿瘤恶性化的密切关系。本研究室关注EMT在肿瘤细胞的迁移、转移、耐药性中的作用及机制以及EMT在肿瘤干细胞分化中发挥的作用

 

近年发表的代表性文章

1. Wang H, Guan F, Chen D, Dou QP#, Yang H#.An analysis of the safety profile of proteasome inhibitors for treating various cancers.Expert Opin Drug Saf. 2014 Aug;13(8):1043-54. doi: 10.1517/14740338.2014.939953. Epub 2014 Jul 9.

2. Nardon C, Schmitt SM, Yang H, Zuo J, Fregona D, Dou QP. Gold(III)-dithiocarbamato peptidomimetics in the forefront of the targeted anticancer therapy: preclinical studies against human breast neoplasia. PLoS One. 2014;9(1):e84248. doi: 10.1371/journal.pone.0084248.

3. Yang H, Wang Y, Cheryan VT, Wu W, Cui CQ, Polin LA, Pass HI, Dou QP, Rishi AK, Wali A. Withaferin a inhibits the proteasome activity in mesothelioma in vitro & in vivo. PLoS One. 2012;7(8):e41214. Epub 2012 Aug 17.

4. Frezza M, Yang H, Dou QP. Modulation of the tumor cell death pathway by androgen receptor in response to cytotoxic stimuli. J Cell Physiol. 2011;226(11):2731-9.

5. Chen D, Wan SB, Yang H, Chan TH, Dou QP. EGCG , green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatment. Adv Clin Chem 2011;53:155-77.

6. Yang H#, Lanbis-Piwowar K, Chan TH, Dou QP#. Green tea polyphenols as proteasome inhibitors: implication in chmoprevetion. Curr Cancer Drug Targets 2011 Mar;11(3):296-306.

7. Kanwar J, Mohammad I, Yang H, Huo C, Chan TH, Dou QP. Computational modeling of the potential interactions of the proteasome beta5 subunit and catechol-O-methyltransferase-resistant EGCG analogs. Int J Mol Med 2010 Aug;26(2):209-15.

8. Yang H and Dou QP. Targeting Apoptosis Pathway with Natural Terpenoids: Implications for Treatment of Breast and Prostate Cancer. Current Drug Targets, 2010; 11(6):734-44.

9. Yang H, Liu J, Dou QP. Targeting tumor proteasome with traditional Chinese medicine. Curr Drug Discov Technol. 2010 Mar 1;7(1):46-53.

10. Huo C#, Yang H#, Cui QC, Dou QP, Chan TH. Proteasome inhibition in human breast cancer cells with high catechol-O-methyltransferase activity by green tea polyphenol EGCG analogs. Bioorg Med Chem. 2010 Feb;18(3):1252-8. Epub 2009 Dec 16.

11. Wang Y, Rishi AK, Puliyappadamba VT, Sharma S, Yang H, Tarca A, Ping Dou Q, Lonardo F, Ruckdeschel JC, Pass HI, Wali A. Targeted proteasome inhibition by velcade induces apoptosis in human mesothelioma and breast cancer cell lines. Cancer Chemother Pharmacol. 2009, 66(3):455-66.

12. Yang H, Sun DK, Chen D, Cui QC, Gu YY, Jiang T, Chen W, Wan SB, Dou QP. Antitumor activity of novel fluoro-substituted (-)-epigallocatechin-3-gallate analogs. Cancer Lett. 2010, 292(1):48-53.

13. Huo C#, Yang H#, Cui QC, Dou QP, Chan TH. Proteasome inhibition in human breast cancer cells with high catechol-O-methyltransferase activity by green tea polyphenol EGCG analogs. Bioorg Med Chem. 2009 Dec 16. [Epub ahead of print]

14. Yang H, Zonder JA, Dou QP. Clinical development of novel proteasome inhibitors for cancer treatment. Expert Opin Investig Drugs. 2009 Jul;18(7):957-71.

15. Huanjie Yang, Ping Zhou, Hongbiao Huang, Di Chen, Ningfang Ma, Cindy Qiuzhi Cui, Shouxing Shen, Weihua Dong, Xiaoyan Zhang, Wen Lian, Xuejun Wang, Q. Ping Dou and Jinbao Liu. Shikonin exerts antitumor activity via proteasome inhibition and cell death induction in vitro&in vivo. Int J Cancer 2009 May 15;124(10):2450-9. (Cover story).

16. Padhye S, Yang H, Jamadar A, Cui QC, Chavan D, Dominiak K, McKinney J, Banerjee S, Dou QP, Sarkar FH. New Difluoro Knoevenagel Condensates of Curcumin, Their Schiff Bases and Copper Complexes as Proteasome Inhibitors and Apoptosis Inducers in Cancer Cells. Pharm Res. 2009 Aug;26(8):1874-80.

17. Huanjie Yang, Shalini Murthy, Fazlul H. Sarkar, Shijie Sheng, G. Prem-Veer Reddy and Q. Ping Dou. Calpain-mediated androgen receptor breakdown in apoptotic prostate cancer cells. J Cell Physiol. 2008 Dec;217(3):569-76.

18. H. Yang, K. R. Landis-Piwowar, D. Chen, V. Milacic, Q. P. Dou. Natural compounds with proteasome inhibitory activity for cancer prevention and treatment. Curr Protein Pept Sci. 2008 Jun;9(3):227-39.

19. Lihua Li, Huanjie Yang, Di Chen, Cindy Cui and Q. Ping Dou. Disulfiram promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity in human cancer cells. Toxicol Appl Pharmacol. 2008 Jun 1;229(2):206-214.

20. Huanjie Yang, Kristin Landis-Piwowar, Dayan Lu, Ying Yuan, Lihua Li, G. Prem-Veer Reddy, Xiao Yuan, Q. Ping Dou. Pristimerin induces apoptosis by targeting the proteasome in prostate cancer cells. J Cell Biochem. 2008 Jan 1;103(1):234-44.

21. Xiaohua Li, Di Chen, Shuping Yin , Yonghong Meng , Huanjie Yang , Kristin R. Landis-Piwowar, Yiwei Li , Fazlul H. Sarkar , G. Prem Veer Reddy, Q. Ping Dou , Shijie Sheng. p38 mitogen-activated protein kinase-dependent Maspin induction positively feeds back on proteasome inhibitor-mediated prostate tumor apoptosis. J Cell Physiol. 2007 Aug;212(2):298-306.

22. Huanjie Yang, Guoqing Shi, and Q. Ping Dou. The Tumor Proteasome Is a Primary Target for the Natural Anticancer Compound Withaferin A Isolated from “Indian Winter Cherry”. Mol Pharmacol. 2007 Feb;71(2):426-37.  

23. Di Chen, Qiuzhi Cindy Cui, Huanjie Yang, Raul A. Barrea, Fazlul H. Sarkar, Shijie Sheng, Bing Yan, G. Prem Veer Reddy and Q. Ping Dou. Clioquinol, a therapeutic agent for Alzheimer’s Disease, has proteasome-inhibitory, androgen receptor suppressing, apoptosis-inducing and anti-tumor activities in human prostate cancer cells and xenografts. Cancer Res. 2007 Feb;15;67(4):1636-44.

24. Di Chen, Marina S. Chen, Qiuzhi Cindy Cui, Huanjie Yang, Q. Ping Dou. Structure-proteasome-inhibitory activity relationships of dietary flavonoids in human cancer cells. Front Biosci. 2007 Jan;12:1935-45.

25. Kristin Landis-Piwowar, Vesna Milacic, Di Chen, Huanjie Yang, Yufeng Zhao, Tak Hang Chan, Bing Yan and Q. Ping Dou. The proteasome as a potential target for novel anticancer drugs and chemosensitizers. Drug Resist Updat. 2006 Dec;9(6):263-73.

26. Di Chen, Qiuzhi Cindy Cui, Huanjie Yang, Q. Ping Dou. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 2006 Nov;66(21):10425-33.

27. Huanjie Yang, Di Chen, Qiuzhi Cindy Cui, Xiao Yuan, Q. Ping Dou. Celastrol, a triterpene extracted from the Chinese “Thunder of God Vine,” is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res. 2006 May;66(9): 4758-65. (Cover story)

近年代表性课题(总经费185万元) 

1. 蛋白酶体靶向抗癌药的筛选及其机制研究 哈尔滨工业大学海内外引进人才科研启动项目(2010. 10-2013. 10)

2. 抗癌药的筛选及其抗癌机理研究与研究方向建设 哈尔滨工业大学985学科(学术)后备带头人培育项目(2010. 12-2013. 12)

3. 新型蛋白酶体抑制剂的筛选与抗肿瘤作用的研究 哈尔滨市科技创新人才研究专项资金项目 (2012.01-2014.12)

4. 蛋白降解途径在前列腺癌化疗耐药性中的作用机制研究 哈工大科研创新基金(2013.05-2015.05)

5. 蛋白酶体抑制剂在前列腺癌细胞诱导自噬的机理分析 留学回国人员科研启动基金(2014.01-2016.12)

6. AR通过转录激活miR-101抑制蛋白酶体抑制剂诱导的自噬 黑龙江省自然科学基金(2014.07.01-2017.07.01)

7. 蛋白酶体活性抑制下自噬调控前列腺癌细胞多西紫杉醇化疗敏感性研究 教育部“春晖计划”合作科研项目(2014.10-2016.10)