收藏 | 手机打开

A Plant Natural Compound(Shikonin) with 4-Hydroxytamoxifen Synergistically Inhibits the Proliferation of Breast Cancer Cells through Activating Apoptosis Signaling Pathway in Vitro and in Vivo

LIN Hongyan  HE Deliu  HAN Hongwei  SUN Wenxue  FENG Lu  MA Yingying  YANG Minkai  LU Guihua  WANG Xiaoming  LU Guihua  QI Jinliang  YANG Yonghua  
【摘要】:4-Hydroxytamoxifen(4-OHT) is the first line of endocrine therapy for estrogen receptor positive(ER+) breast cancer patients. However, its efficacy was greatly reduced by triggering drug resistance to ER+ patients and insensitivity to estrogen receptor negative(ER-) patients, which reinforcing the need for discovery of new effective chemosensitization agents to 4-OHT. Shikonin(SK) is a plant natural product broadly explored in cancer therapy. In the current study, we are aiming to assess the combination effects of SK and 4-OHT on human breast cancer cells in vitro and in vivo, and investigate the underlying mechanisms. Through in vitro experiment, we found that SK and 4-OHT synergistically inhibited cell proliferation in both MCF-7 and MDA-MB-435 S cells and promoted apoptosis by reducing mitochondrial membrane potential and increasing intracellular reaction oxygen species(ROS) level. Western blot results demonstrated that the combination of SK and 4-OHT activated both the mitochondrial-dependent apoptosis and the death receptor pathway, significantly regulating the PI3 K/AKT/Caspase 9 signaling pathway. Further, compared with SK and 4-OHT alone, the combination of SK and 4-OHT could better inhibit the tumor growth in the xenograft model of nude mice. Our findings suggest that the combination of SK and 4-OHT is of great potential to achieve a more highly efficient anticancer effect in breast cancer therapy. SK may be a promising candidate as an adjuvant agent to 4-OHT for breast cancer treatments.

中国期刊全文数据库 前20条
1 李荣山;丁涛;刘晓城;李彩霞;;Influence of SB203580 on Cell Apoptosis and P38MAPK in Renal Ischemia/Reperfusion Injury[J];华中科技大学学报(医学英德文版);2006年01期
2 ;Docetaxel Influences Autocrine of Transforming Growth Factors and Induces Apoptosis in Human Ovarian Cancer Cell Line AO[J];Chinese Medical Sciences Journal;2006年03期
3 ;Effect of Thrombin on the Apoptosis of Hippocampal Neurons in vitro[J];Wuhan University Journal of Natural Sciences;2005年03期
4 ;Trihydroxybenzoic Acid Dimer-induced Apoptosis Effects in vitro[J];Chemical Research in Chinese Universities;2005年04期
5 姚颖,田兴奎,刘晓城,邵菊芳,吕永曼;The p53-mediated Apoptosis in Hypercholesterolemia-induced Renal Injury of Rats[J];华中科技大学学报(医学英德文版);2005年04期
6 ;Involvement of Oxidative Stress and Down-Regulation of Bcl-2 in Arachidonic Acid-Induced Apoptosis in HUVECs[J];Wuhan University Journal of Natural Sciences;2005年06期
7 扈盛;;Apoptosis of Cancer Cells Induced by HAP Nanoparticles[J];Journal of Wuhan University of Technology-Materials Science;2005年04期
8 叶亮,杜心灵,夏家红,江平;Effects of rHu-EPO on Myocyte Apoptosis and Cardiac Function Following Acute Myocardial Infarction in Rats[J];华中科技大学学报(医学英德文版);2005年01期
9 ;Apoptosis is involved in the cardiac damage induced by singaortic denervation in rats[J];第二军医大学学报;2004年01期
10 秦莉,王西明,段秋红,陈蓓蓓,何善述;Inhibitory Effect of Melatonin on the Growth of H22 Hepatocarcinoma Cells by Inducing Apoptosis[J];华中科技大学学报(医学英德文版);2004年01期
11 陈燕,胡东;Effects of POH in Combination with STI571 on the Proliferation and Apoptosis of K562 Cells[J];华中科技大学学报(医学英德文版);2004年01期
12 曹阳,魏厚仁,Pfaffl Michael,笪邦红,李忠玉;Apoptosis of Human Trabecular Meshwork Cells Induced by Transforming Growth Factor-β_2 in vitro[J];华中科技大学学报(医学英德文版);2004年01期
13 朱遂强,唐洲平,郭守刚,彭岚,方思羽,张苏明;Experimental Study on the Expression of HIF-1α and Its Relationship to Apoptosis in Tissues around Cerebral Bleeding Loci[J];华中科技大学学报(医学英德文版);2004年04期
14 ;Effect of High Dosage of Methylprednisolone on Rat Retinal Ganglion Cell Apoptosis after Optic Nerve Crush[J];眼科学报;2004年03期
15 俞琳琳,刘洋,崔永华;Expression of Hypoxia Inducible Factor-1α and Its Relationship to Apoptosis and Proliferation in Human Laryngeal Squamous Cell Carcinoma[J];华中科技大学学报(医学英德文版);2004年06期
16 陈雯,王智,张缨;The Effect of Zinc on the Apoptosis of Cultured Human Retinal Pigment Epithelial Cells[J];华中科技大学学报(医学英德文版);2003年04期
17 钱玲梅,王笑云,冷静;Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine[J];Journal of Nanjing Medical University;2002年01期
18 周林福,殷凯生;Effect of Arsenic Trioxide on Apoptosis of Pulmonary Eosinophile in Asthmatic Guinea-Pigs[J];Chinese Journal of Integrated Traditional and Western Medicine;2002年02期
19 赵东强 ,修贺明 ,姜慧卿 ,张晓岚;Study on Effect of IH764-3, an Active Principle of Salviae miltiorrhizae, in Inducing Hepatic Stellate Cell Apoptosis[J];Chinese Journal of Integrated Traditional and Western Medicine;2002年02期
20 ;Cerebral Apoptosis Gene Expression on Rats with Passive Smoking from Intrauterine to Weaning[J];中国当代儿科杂志;2001年04期
中国重要会议论文全文数据库 前10条
1 LIN Hongyan;HE Deliu;HAN Hongwei;SUN Wenxue;FENG Lu;MA Yingying;YANG Minkai;LU Guihua;WANG Xiaoming;LU Guihua;QI Jinliang;YANG Yonghua;;A Plant Natural Compound(Shikonin) with 4-Hydroxytamoxifen Synergistically Inhibits the Proliferation of Breast Cancer Cells through Activating Apoptosis Signaling Pathway in Vitro and in Vivo[A];江苏省遗传学会2019年学术研讨会论文集[C];2019年
2 Xiao-Mei Mao;Qi-Rui Fu;Hua-Liang Li;Ya-Hui Zheng;Shu-Ming Chen;Xin-Yi Hu;Qiong-Hua Chen;Qing-Xi Chen;;Crocodile Choline Induces Apoptosis of Human Gastric Cancer BGC823 Cells[A];中国生物化学与分子生物学会2016年全国学术会议论文集[C];2016年
3 Ching-Yuan Wu;Yin-yin Lin;;Ethanol Extracts of Antrodia Cinnamomea Suppress the Growth of Human Prostate Cancer Cells by Inducing S Phase Arrest and Apoptosis[A];第十四届全国中药和天然药物学术研讨会论文摘要[C];2014年
4 Betty Yuen Kwan Law;Liang Liu;Vincent Kam Wai Wong;;Natural Alkaloids Induce Autophagy and Autophagy Cell Death in Apoptosis-resistant Cells[A];第十四届全国中药和天然药物学术研讨会论文摘要[C];2014年
5 ;Effect of Propofol on Nuclear Factor-κB Signal Pathway and Cardiomyocytes Apoptosis in Myocardium Ischemia/Reperfusion Injury in Rats[A];中国药理学会第十次全国学术会议专刊[C];2009年
6 盛辉;陈胜广;程晓芸;盛春君;张戈;徐罡;吴国亭;秦岭;;Rosiglitazone Induces Osteoblasts Apoptosis via the Activation of GSK3 β[A];2009中华医学会骨质疏松症中青年学者论坛论文集[C];2009年
7 ;Survivin Sirna Transfected With A Microbubble And Ultrasound Technique Induces Apoptosis In Ovarian Cancer Cells[A];第四届长三角妇产科学术论坛暨浙江省2009年妇产科学术年会论文汇编[C];2009年
8 ;Conjugated Polymers as Multifunctional Biomedical Platforms:Anticancer Activity and Apoptosis Imaging[A];第一届全国生物物理化学会议暨生物物理化学发展战略研讨会论文摘要集[C];2010年
9 郭晓莹;;Protective Effects of BMP-7 on Osteoblast Apoptosis Induced by Gingipains[A];中华口腔医学会第14次全国口腔医学学术会议(2012年会)论文汇编[C];2012年
10 ;Tea Polyphenols Induce Apoptosis and Inhibit Proliferation in NFC Cells and the Mechanism Involved[A];2000全国肿瘤学术大会论文集[C];2000年
中国博士学位论文全文数据库 前2条
1 KHALIL LAFI ALJABARIN;[D];华中科技大学;2014年
2 郦剑勇;苯并噻唑抗肿瘤药物的合成、筛选及其作用机理[D];浙江大学;2010年
中国硕士学位论文全文数据库 前2条
1 刘文辉;皮肤扩张早期miRNA和mRNA的变化及关键miRNA筛选[D];上海交通大学;2015年
2 樊瑞利;传染病动力学及其稳定性分析[D];中国地质大学;2014年
 快捷付款方式  订购知网充值卡  订购热线  帮助中心
  • 400-819-9993
  • 010-62982499
  • 010-62783978