Shikonin inhibits invasiveness of osteosarcoma through MMP13 suppression

被引:21
作者
Deng, Biyong [1 ]
Qiu, Bing [1 ]
机构
[1] Guizhou Prov Osteol Hosp, Dept Orthoped, Guiyang 550007, Peoples R China
关键词
Osteosarcoma (OS); Shikonin; Matrix metalloproteinase (MMP)-13; CELL-MIGRATION; TUMOR-SUPPRESSOR; DOWN-REGULATION; IN-VITRO; INVASION; PROLIFERATION; EXPRESSION; PATHWAY; DIFFERENTIATION; APOPTOSIS;
D O I
10.1007/s13277-015-3662-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Osteosarcoma (OS) is the most common primary malignant bone tumor, notorious for its metastasis. We have recently shown that shikonin, an effective constituent extracted from Chinese medicinal herb, induces necroptosis in OS cells. Nevertheless, the effects of low-dose shikonin on the invasiveness of OS cells are unknown. Here, we showed that shikonin dose-dependently decreased OS cell invasiveness in both scratch wound healing assay and transwell cell migration assay. Moreover, the direct target of shikonin on cell invasiveness was found to be matrix metalloproteinase (MMP)-13. Further, the inhibitory effects of shikonin on cell invasiveness were completely abolished in MMP13-overexpressing OS cells. Together, these data suggest that shikonin may suppress OS invasiveness through MMP13 suppression. Thus, our data highlight a previous unappreciated role for shikonin in suppressing OS cell metastasis.
引用
收藏
页码:9311 / 9317
页数:7
相关论文
共 38 条
[1]   Traditional Chinese Medicine Remedy to Jury: The Pharmacological Basis for the Use of Shikonin as an Anticancer Therapy [J].
Andujar, I. ;
Recio, M. C. ;
Giner, R. M. ;
Rios, J. L. .
CURRENT MEDICINAL CHEMISTRY, 2013, 20 (23) :2892-2898
[2]   Pharmacological Properties of Shikonin - A Review of Literature since 2002 [J].
Andujar, Isabel ;
Luis Rios, Jose ;
Maria Giner, Rosa ;
Carmen Recio, Maria .
PLANTA MEDICA, 2013, 79 (18) :1685-1697
[3]   Liver X Receptor α Inhibits Osteosarcoma Cell Proliferation through Up-Regulation of FoxO1 [J].
Chang, Yue-wen ;
Zhao, Yong-fang ;
Cao, Yue-long ;
Gu, Xin-feng ;
Li, Zhi-qiang ;
Wang, Shu-qiang ;
Miao, Jin-hao ;
Zhan, Hong-sheng .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2013, 32 (01) :180-186
[4]   A New Synthetic Ursolic Acid Derivative IUA with Anti-Tumor Efficacy Against Osteosarcoma Cells via Inhibition of JNK Signaling Pathway [J].
Chen, Jian ;
Fu, Haijian ;
Wang, Zhuoying ;
Yin, Fei ;
Li, Jianxin ;
Hua, Yingqi ;
Cai, Zhengdong .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2014, 34 (03) :724-733
[5]   The E-F Hand Calcium-Binding Protein S100A4 Regulates the Proliferation, Survival and Differentiation Potential of Human Osteosarcoma Cells [J].
Chen, Xian ;
Luther, Gaurav ;
Zhang, Wenwen ;
Nan, Guoxin ;
Wagner, Eric R. ;
Liao, Zhan ;
Wu, Ningning ;
Zhang, Hongmei ;
Wang, Ning ;
Wen, Sheng ;
He, Yunfeng ;
Deng, Fang ;
Zhang, Junhui ;
Wu, Di ;
Zhang, Bosi ;
Haydon, Rex C. ;
Zhou, Lan ;
Luu, Hue H. ;
He, Tong-Chuan .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2013, 32 (04) :1083-1096
[6]   Bufalin-Inhibited Migration and Invasion in Human Osteosarcoma U-2 OS Cells Is Carried Out by Suppression of the Matrix Metalloproteinase-2, ERK, and JNK Signaling Pathways [J].
Chueh, Fu-Shin ;
Chen, Ya-Yin ;
Huang, An-Cheng ;
Ho, Heng-Chien ;
Liao, Ching-Lung ;
Yang, Jai-Sing ;
Kuo, Chao-Lin ;
Chung, Jing-Gung .
ENVIRONMENTAL TOXICOLOGY, 2014, 29 (01) :21-29
[7]   Molecular mechanisms of glioma cell migration and invasion [J].
Demuth, T ;
Berens, ME .
JOURNAL OF NEURO-ONCOLOGY, 2004, 70 (02) :217-228
[8]   Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling [J].
Enomoto, M. ;
Hayakawa, S. ;
Itsukushima, S. ;
Ren, D. Y. ;
Matsuo, M. ;
Tamada, K. ;
Oneyama, C. ;
Okada, M. ;
Takumi, T. ;
Nishita, M. ;
Minami, Y. .
ONCOGENE, 2009, 28 (36) :3197-3208
[9]   The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis [J].
Fu, Zeze ;
Deng, Biyong ;
Liao, Yuxin ;
Shan, Liancheng ;
Yin, Fei ;
Wang, Zhuoying ;
Zeng, Hui ;
Zuo, Dongqing ;
Hua, Yingqi ;
Cai, Zhengdong .
BMC CANCER, 2013, 13
[10]   EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma [J].
Futamura, Naohisa ;
Nishida, Yoshihiro ;
Urakawa, Hiroshi ;
Kozawa, Eiji ;
Ikuta, Kunihiro ;
Hamada, Shunsuke ;
Ishiguro, Naoki .
TUMOR BIOLOGY, 2014, 35 (06) :5159-5165