Oridonin Promotes Apoptosis and Restrains the Viability and Migration of Bladder Cancer by Impeding TRPM7 Expression via the ERK and AKT Signaling Pathways

被引:18
作者
Che, Xianping [1 ]
Zhan, Jiangtao [1 ]
Zhao, Fan [1 ]
Zhong, Zunhe [1 ]
Chen, Mianchuan [1 ]
Han, Ruifa [2 ]
Wang, Yi [1 ]
机构
[1] Hainan Med Univ, Affiliated Hosp 2, Dept Urol, Haikou 570311, Hainan, Peoples R China
[2] Tianjin Med Univ, Tianjin Inst Urol, Hosp 2, Dept Urol, Tianjin 300211, Peoples R China
关键词
OVARIAN-CANCER; PROLIFERATION; CELLS; OVEREXPRESSION; IMMUNOTHERAPY; METASTASIS; PROGNOSIS; INVASION; CHANNELS; THERAPY;
D O I
10.1155/2021/4340950
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background. Oridonin is a powerful anticancer compound found in Rabdosia rubescens. However, its potential impact on bladder cancer remains uninvestigated. In this work, we aimed to detect the anticancer effect of oridonin on bladder cancer and explore the molecular mechanisms involved. Methods. The anticancer activity of oridonin was assessed in vitro with a CCK8 assay, an annexin V-FITC apoptosis analysis, and colony formation and Transwell migration assays which were performed with the human bladder cancer cell line T24. Levels of apoptosis-related proteins, melastatin transient receptor potential channel 7 (TRPM7), and signaling molecules were examined in oridonin-treated T24 cells by western blotting or RT-PCR. Oridonin anticancer efficacy was further validated in vivo with a T24 xenograft mouse model. Results. Oridonin repressed the proliferative, colony-forming, and migratory capacities of T24 cells, triggered extensive apoptosis in vitro, and retarded tumor growth in vivo. Moreover, oridonin treatment significantly increased expression levels of p53 and cleaved caspase-3 and reduced expression of TRPM7, p-AKT, and p-ERK. Conclusion. Oridonin exhibited outstanding antiproliferative and antimigratory effects on bladder cancer, and these effects were at least partially associated with targeting of TRPM7 through inactivation of the ERK and AKT signaling pathways. These findings provide insight for the clinical application of oridonin in bladder cancer prevention.
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页数:9
相关论文
共 39 条
[1]   TRPM7 senses oxidative stress to release Zn2+ from unique intracellular vesicles [J].
Abiria, Sunday A. ;
Krapivinsky, Grigory ;
Sah, Rajan ;
Santa-Cruz, Ana G. ;
Chaudhuri, Dipayan ;
Zhang, Jin ;
Adstamongkonkul, Pichet ;
DeCaen, Paul G. ;
Clapham, David E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (30) :E6079-E6088
[2]   Role of ion channels in gastrointestinal cancer [J].
Anderson, Kyle J. ;
Cormier, Robert T. ;
Scott, Patricia M. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2019, 25 (38) :5732-5772
[3]   Prospects and progress of immunotherapy for bladder cancer [J].
Boegemann, Martin ;
Aydin, Ahmet Murat ;
Bagrodia, Aditya ;
Krabbe, Laura-Maria .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2017, 17 (11) :1417-1431
[4]   Decreased TRPM7 inhibits activities and induces apoptosis of bladder cancer cells via ERK1/2 pathway [J].
Cao, Rui ;
Meng, Zhe ;
Liu, Tongzu ;
Wang, Gang ;
Qian, Guofeng ;
Cao, Tingting ;
Guan, Xinyuan ;
Dan, Hancai ;
Xiao, Yu ;
Wang, Xinghuan .
ONCOTARGET, 2016, 7 (45) :72941-72960
[5]   Functional TRPV and TRPM channels in human preadipocytes [J].
Che, Hui ;
Yue, Jianbo ;
Tse, Hung-Fat ;
Li, Gui-Rong .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2014, 466 (05) :947-959
[6]   The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression [J].
Chen, Jiandong .
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2016, 6 (03)
[7]   Inhibition of TRPM7 by carvacrol suppresses glioblastoma cell proliferation, migration and invasion [J].
Chen, Wen-Liang ;
Barszczyk, Andrew ;
Turlova, Ekaterina ;
Deurloo, Marielle ;
Liu, Baosong ;
Yang, Burton B. ;
Rutka, James T. ;
Feng, Zhong-Ping ;
Sun, Hong-Shuo .
ONCOTARGET, 2015, 6 (18) :16321-16340
[8]   Assessment of TRPM7 functions by drug-like small molecules [J].
Chubanov, Vladimir ;
Ferioli, Silvia ;
Gudermann, Thomas .
CELL CALCIUM, 2017, 67 :166-173
[9]   Caspases: the executioners of apoptosis [J].
Cohen, GM .
BIOCHEMICAL JOURNAL, 1997, 326 :1-16
[10]   TRPM7 channel regulates PDGF-BB-induced proliferation of hepatic stellate cells via PI3K and ERK pathways [J].
Fang, Ling ;
Zhan, Shuxiang ;
Huang, Cheng ;
Cheng, Xi ;
Lv, Xiongwen ;
Si, Hongfang ;
Li, Jun .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2013, 272 (03) :713-725