Baicalein inhibits progression of osteosarcoma cells through inactivation of the Wnt/β-catenin signaling pathway

被引:35
作者
Dai, Guo [1 ]
Zheng, Di [1 ]
Wang, Qianliang [2 ]
Yang, Jian [1 ]
Liu, Gaiwei [1 ]
Song, Qi [1 ]
Sun, Xiangran [1 ]
Tao, Chunjie [1 ]
Hu, Qingzhu [1 ]
Gao, Tian [3 ]
Yu, Ling [1 ]
Guo, Weichun [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Orthoped, Wuhan 430060, Hubei, Peoples R China
[2] Wuhan Univ, Renmin Hosp, Dept Urol Surg, Wuhan 430060, Hubei, Peoples R China
[3] Peking Univ, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ,Dept Orthoped Oncol, Beijing, Peoples R China
关键词
baicalein; osteosarcoma; proliferation; apoptosis; Wnt signaling pathway; TRADITIONAL CHINESE MEDICINE; BREAST-CANCER; CYCLE ARREST; IN-VITRO; SUPPRESSES; PROLIFERATION; EXPRESSION; GROWTH; METASTASIS; ACTIVATION;
D O I
10.18632/oncotarget.20987
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Osteosarcoma is a very common type of malignant bone tumor in children and young adults and aberrant activation of Wnt/beta-catenin signaling pathway has been discovered in osteosarcoma. The traditional Chinese medicine baicalein was proved to have anti-proliferative and anti-metastatic properties in osteosarcoma, but the mechanism remained poorly understood. In the present study, we assessed the effects of baicalein on osteosarcoma and detected the potential molecular mechanism. We found that baicalein significantly suppressed the proliferation of osteosarcoma cells in a concentration-and time-dependent manner. In additional, baicalein could induce apoptosis and cell cycle arrest and reduce cell motility. Moreover, the level of beta-catenin and its target genes, including c-myc, cyclinD1, and survivin significantly decreased in baicalein-treated osteosarcoma cells, whereas exogenous expression of beta-catenin could reverse the anti-proliferative and anti-metastatic effects of baicalein. Subsequently, we established a 143B xenograft tumor model and found that baicalein treatment significantly inhibited tumor growth accompanied with inhibiting Wnt/beta-catenin pathway. Thus, these findings suggest that baicalein may be a potentially effective Chinese herbal medicine for therapeutics of osteosarcoma and Wnt/beta-catenin signaling pathway may serve as an efficient molecular marker or predictive target for osteosarcoma.
引用
收藏
页码:86098 / 86116
页数:19
相关论文
共 60 条
[1]   WNT signalling pathways as therapeutic targets in cancer [J].
Anastas, Jamie N. ;
Moon, Randall T. .
NATURE REVIEWS CANCER, 2013, 13 (01) :11-26
[2]   Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells [J].
Bie, Beibei ;
Sun, Jin ;
Li, Jun ;
Guo, Ying ;
Jiang, Wei ;
Huang, Chen ;
Yang, Jun ;
Li, Zongfang .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2017, 41 (04) :1519-1531
[3]   Wnt Pathway in Osteosarcoma, from Oncogenic to Therapeutic [J].
Cai, Yu ;
Cai, Tiange ;
Chen, Yan .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2014, 115 (04) :625-631
[4]   Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells [J].
Chen, Changbao ;
Zhao, Meng ;
Tian, Aixian ;
Zhang, Xiaolin ;
Yao, Zhi ;
Ma, Xinlong .
ONCOTARGET, 2015, 6 (19) :17570-17583
[5]   Exploring therapeutic potentials of baicalin and its aglycone baicalein for hematological malignancies [J].
Chen, Haijun ;
Gao, Yu ;
Wu, Jianlei ;
Chen, Yingyu ;
Chen, Buyuan ;
Hu, Jianda ;
Zhou, Jia .
CANCER LETTERS, 2014, 354 (01) :5-11
[6]   Integrins and metastasis [J].
Ganguly, Kirat Kumar ;
Pal, Sekhar ;
Moulik, Shuvojit ;
Chatterjee, Amitava .
CELL ADHESION & MIGRATION, 2013, 7 (03) :251-261
[7]   A monoclonal antibody against the Wnt signaling inhibitor dickkopf-1 inhibits osteosarcoma metastasis in a preclinical model [J].
Goldstein, Seth D. ;
Trucco, Matteo ;
Guzman, Wendy Bautista ;
Hayashi, Masanori ;
Loeb, David M. .
ONCOTARGET, 2016, 7 (16) :21114-21123
[8]   Molecular interplay between cdk4 and p21 dictates G0/G1 cell cycle arrest in prostate cancer cells [J].
Gulappa, Thippeswamy ;
Reddy, Ramadevi Subramani ;
Suman, Suman ;
Nyakeriga, Alice M. ;
Damodaran, Chendil .
CANCER LETTERS, 2013, 337 (02) :177-183
[9]   Advances in emerging drugs for osteosarcoma [J].
Hattinger, Claudia Maria ;
Fanelli, Marilu ;
Tavanti, Elisa ;
Vella, Serena ;
Ferrari, Stefano ;
Picci, Piero ;
Serra, Massimo .
EXPERT OPINION ON EMERGING DRUGS, 2015, 20 (03) :495-514
[10]   Baicalein suppresses the viability of MG-63 osteosarcoma cells through inhibiting c-MYC expression via Wnt signaling pathway [J].
He, Nengbin ;
Zhang, Zhichang .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2015, 405 (1-2) :187-196