Aclidinium bromide inhibits human glioma cell proliferation, migration and invasion and promotes apoptosis via the PI3K/AKT signaling pathway

被引:6
作者
Huang, S. H. [1 ]
Zhang, T. [1 ]
Zhao, C. G. [2 ]
Qin, J. [1 ]
Qi, P. [3 ]
Li, F. T. [1 ]
He, X. J. [1 ]
机构
[1] Xi An Jiao Tong Univ, Dept Orthoped, Affiliated Hosp 2, Xian, Shaanxi, Peoples R China
[2] Fourth Mil Med Univ, Xijing Hosp, Xian, Shaanxi, Peoples R China
[3] Med Univ Air Force, Tangdu Hosp, Xian, Shaanxi, Peoples R China
关键词
aclidinium bromide; glioblastoma; proliferation; migration; invasion; apoptosis; GLIOBLASTOMA FORMATION; CANCER; RAS; TEMOZOLOMIDE; TRANSITION; EXPRESSION; GROWTH; TRIAL; AKT;
D O I
10.4149/neo_2018_171117N705
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This study investigates the anti-cancer potential of Aclidinium bromide (INN) in glioblastoma. Glioblastoma cell lines U251 and U87 were treated with INN and its effects on cell migration and invasion were assessed by transwell migration and invasion assays., The effects of INN on proliferation and apoptosis were detected by CCK-8 kit and flow cytometry, and Western blotting determined anti-apoptotic proteins and signaling pathway changes. The results show that INN effectively suppressed proliferation, migration and invasion and induced apoptosis in U251 and U87 cells, respectively. Furthermore, the expression levels of the Bcl-2 anti-apoptotic protein was significantly decreased while Bax and caspase-3 expression were both increased in glioblastoma cells (all, p<0.05). Moreover, INN inactivated the PI3K/AKT signaling pathway by down-regulating the level of p-AKT, p-mTOR, P70 and CydinD1 (all, p<0.05). In conclusion, our data suggests that INN could provide novel anticancer therapy in the treatment of glioblastoma.
引用
收藏
页码:865 / 871
页数:7
相关论文
共 33 条
[1]   Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases [J].
Alagha, Khuder ;
Palot, Alain ;
Sofalvi, Tunde ;
Pahus, Laurie ;
Gouitaa, Marion ;
Tummino, Celine ;
Martinez, Stephanie ;
Charpin, Denis ;
Bourdin, Arnaud ;
Chanez, Pascal .
THERAPEUTIC ADVANCES IN CHRONIC DISEASE, 2014, 5 (02) :85-98
[2]   RETRACTED: Secreted Frizzled-Related Protein 4 Inhibits Glioma Stem-Like Cells by Reversing Epithelial to Mesenchymal Transition, Inducing Apoptosis and Decreasing Cancer Stem Cell Properties (Retracted Article) [J].
Bhuvanalakshmi, G. ;
Arfuso, Frank ;
Millward, Michael ;
Dharmarajan, Arun ;
Warrier, Sudha .
PLOS ONE, 2015, 10 (06)
[3]   The PI3K Pathway As Drug Target in Human Cancer [J].
Courtney, Kevin D. ;
Corcoran, Ryan B. ;
Engelman, Jeffrey A. .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (06) :1075-1083
[4]   RETRACTED: miR-330-5p suppresses glioblastoma cell proliferation and invasiveness through targeting ITGA5 (Retracted Article) [J].
Feng, Linsen ;
Ma, Jianhua ;
Ji, Haiming ;
Liu, Yichun ;
Hu, Weixing .
BIOSCIENCE REPORTS, 2017, 37
[5]   Targeting apoptosis pathways in cancer therapy [J].
Fulda, S ;
Klaus-Michael, D .
CURRENT CANCER DRUG TARGETS, 2004, 4 (07) :569-576
[6]   Role of tumor cell adhesion and migration in organ-specific metastasis formation [J].
Gassmann, P ;
Enns, A ;
Haier, J .
ONKOLOGIE, 2004, 27 (06) :577-582
[7]  
GAVALDA A, 2010, NEW DRUGS TARGETS AS, P33
[8]   The in vitro and in vivo profile of aclidinium bromide in comparison with glycopyrronium bromide [J].
Gavalda, Amadeu ;
Ramos, Israel ;
Carcasona, Carla ;
Calama, Elena ;
Otal, Raquel ;
Luis Montero, Jose ;
Sentellas, Sonia ;
Aparici, Monica ;
Vilella, Dolors ;
Alberti, Joan ;
Beleta, Jorge ;
Miralpeix, Montserrat .
PULMONARY PHARMACOLOGY & THERAPEUTICS, 2014, 28 (02) :114-121
[9]   Characterization of Aclidinium Bromide, a Novel Inhaled Muscarinic Antagonist, with Long Duration of Action and a Favorable Pharmacological Profile [J].
Gavalda, Amadeu ;
Miralpeix, Montserrat ;
Ramos, Israel ;
Otal, Raquel ;
Carreno, Cristina ;
Vinals, Marisa ;
Domenech, Teresa ;
Carcasona, Carla ;
Reyes, Blanca ;
Vilella, Dolors ;
Gras, Jordi ;
Cortijo, Julio ;
Morcillo, Esteban ;
Llenas, Jesus ;
Ryder, Hamish ;
Beleta, Jorge .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2009, 331 (02) :740-751
[10]   The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family [J].
Heath-Engel, H. M. ;
Chang, N. C. ;
Shore, G. C. .
ONCOGENE, 2008, 27 (50) :6419-6433