Matrine inhibits cell proliferation and induces apoptosis of human rhabdomyosarcoma cells via downregulation of the extracellular signal-regulated kinase pathway

被引:9
作者
Yan, Penghui [1 ]
Huang, Zongqiang [1 ]
Zhu, Junbo [1 ]
机构
[1] Zhengzhou Univ, Dept Orthoped, Affiliated Hosp 1, 1 Jianshe Rd, Zhengzhou 450003, Henan, Peoples R China
关键词
rabdomyosarcoma; matrine; proliferation; apoptosis; ERK signaling; IN-VITRO; EMBRYONAL RHABDOMYOSARCOMA; OSTEOSARCOMA CELLS; AUTOPHAGY; INFLAMMATION; GROWTH; VIVO;
D O I
10.3892/ol.2017.6564
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Matrine, extracted from the Chinese traditional medicine Sophorae flavescentis, has been demonstrated to exhibit antitumor effects on numerous types of cancer in vivo and in vitro with low toxicity. However, its antitumor mechanism in rhabdomyosarcoma (RMS) cells remains unclear. In the present study, the antitumor effects of matrine and its underlying mechanisms in RMS were investigated in vitro. The results demonstrated that matrine inhibited cell proliferation, migration and invasion, and induced apoptosis of RMS cells in a dose-dependent manner. Furthermore, the expression levels of phosphorylated mitogen-activated protein kinase (p-MEK) and phosphorylated extracellular signal-regulated kinase (p-ERK) significantly decreased in RMS cells following matrine treatment. In addition, the apoptotic effects of matrine in RMS cells were partially inhibited upon MEK1 overexpression and enhanced upon combined treatment with an ERK inhibitor (U0126). In addition, the ratio of apoptosis regulator BCL-2/BAX significantly decreased following matrine treatment. In conclusion, these findings indicate that matrine inhibits cell proliferation and induces the apoptosis of RMS cells by suppressing the ERK signaling pathway, and may be a novel effective candidate for the treatment of patients with RMS.
引用
收藏
页码:3148 / 3154
页数:7
相关论文
共 25 条
[1]   Molecular diagnostics in the management of rhabdomyosarcoma [J].
Arnold, Michael A. ;
Barr, Fredric G. .
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, 2017, 17 (02) :189-194
[2]  
Belyea Brian, 2012, Sarcoma, V2012, P406239, DOI 10.1155/2012/406239
[3]   Key role of MEK/ERK pathway in sustaining tumorigenicity and in vitro radioresistance of embryonal rhabdomyosarcoma stem-like cell population [J].
Ciccarelli, Carmela ;
Vulcano, Francesca ;
Milazzo, Luisa ;
Gravina, Giovanni Luca ;
Marampon, Francesco ;
Macioce, Giampiero ;
Giampaolo, Adele ;
Tombolini, Vincenzo ;
Di Paolo, Virginia ;
Hassan, Hamisa Jane ;
Zani, Bianca Maria .
MOLECULAR CANCER, 2016, 15
[4]   Synthetic lethal interaction between PI3K/Akt/mTOR and Ras/MEK/ERK pathway inhibition in rhabdomyosarcoma [J].
Guenther, Monika Katharina ;
Graab, Ulrike ;
Fulda, Simone .
CANCER LETTERS, 2013, 337 (02) :200-209
[5]   Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes [J].
Herrero, Ana ;
Pinto, Adan ;
Colon-Bolea, Paula ;
Casar, Berta ;
Jones, Mary ;
Agudo-Ibanez, Lorena ;
Vidal, Rebeca ;
Tenbaum, Stephan P. ;
Nuciforo, Paolo ;
Valdizan, Elsa M. ;
Horvath, Zoltan ;
Orfi, Laszlo ;
Pineda-Lucena, Antonio ;
Bony, Emilie ;
Keri, Gyorgy ;
Rivas, German ;
Pazos, Angel ;
Gozalbes, Rafael ;
Palmer, Hector G. ;
Hurlstone, Adam ;
Crespo, Piero .
CANCER CELL, 2015, 28 (02) :170-182
[6]   Rhabdomyosarcoma: Current Challenges and Their Implications for Developing Therapies [J].
Hettmer, Simone ;
Li, Zhizhong ;
Billin, Andrew N. ;
Barr, Frederic G. ;
Cornelison, D. D. W. ;
Ehrlich, Alan R. ;
Guttridge, Denis C. ;
Hayes-Jordan, Andrea ;
Helman, Lee J. ;
Houghton, Peter J. ;
Khan, Javed ;
Langenau, David M. ;
Linardic, Corinne M. ;
Pal, Ranadip ;
Partridge, Terence A. ;
Pavlath, Grace K. ;
Rota, Rossella ;
Schaefer, Beat W. ;
Shipley, Janet ;
Stillman, Bruce ;
Wexler, Leonard H. ;
Wagers, Amy J. ;
Keller, Charles .
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2014, 4 (11)
[7]  
Li HJ, 2015, INT J CLIN EXP PATHO, V8, P14793
[8]   Matrine inhibits the invasive properties of human osteosarcoma cells by downregulating the ERK-NF-κB pathway [J].
Li, Yi ;
Zhang, Zhen-Ni ;
Zhao, Hong-Mou ;
Tong, Zhi-Chao ;
Yang, Jie ;
Wang, Hu ;
Liang, Xiao-Jun .
ANTI-CANCER DRUGS, 2014, 25 (09) :1035-1043
[9]   Anti-tumor activities of matrine and oxymatrine: literature review [J].
Liu, Yan ;
Xu, Yang ;
Ji, Weidan ;
Li, Xiaoya ;
Sun, Bin ;
Gao, Quangen ;
Su, Changqing .
TUMOR BIOLOGY, 2014, 35 (06) :5111-5119
[10]   Matrine-induced autophagy counteracts cell apoptosis via the ERK signaling pathway in osteosarcoma cells [J].
Ma, Kun ;
Huang, Man-Yu ;
Guo, Yan-Xing ;
Hu, Guo-Qiang .
ONCOLOGY LETTERS, 2016, 12 (03) :1854-1860