Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer

被引:154
作者
Zhang, Hui [1 ,2 ]
Zhang, Xuan [3 ]
Li, Xun [1 ,2 ]
Meng, Wen-Bo [1 ,2 ]
Bai, Zhong-Tian [1 ,2 ]
Rui, Shao-Zhen [1 ,2 ]
Wang, Zheng-Feng [1 ,2 ]
Zhou, Wen-Ce [1 ,2 ]
Jin, Xiao-Da [4 ]
机构
[1] Lanzhou Univ, Hosp 1, Dept Gen Surg 2, Inst Hepatopancreatobiliary Surg, Lanzhou, Gansu, Peoples R China
[2] Key Lab Biotherapy & Regenerat Med Gansu Prov, Lanzhou, Gansu, Peoples R China
[3] Northwest Minzu Univ, Lanzhou, Gansu, Peoples R China
[4] Univ South China, Hengyang, Peoples R China
关键词
apoptosis; CCNB1; cell cycle; gene silencing; p53 signaling pathway; pancreatic cancer; senescence; EXPRESSION; ACTIVATION; B1; PROLIFERATION; EPIDEMIOLOGY; CASPASES; GROWTH; OVEREXPRESSION; PROGRESSION; SURVIVAL;
D O I
10.1002/jcp.26816
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Pancreatic cancer (PC) is a serious malignancy with high mortality and poor prognosis due to nonspecific incipient symptoms and early metastasis. Also, increasing evidence indicates that a panel of genes is newly identified in the pathogenesis of PC. As is a regulatory subunit, elevated cyclin B1 (CCNB1) expression has been detected in different cancers including PC. This study is designed to investigate the effects of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in PC. PC tissues and normal pancreatic tissues were collected. Cells were transfected and assigned into different groups. The expressions of CCNB1, p53, MDM2, Bax, caspase-9, caspase-3, and p21 in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. beta-Galactosidase staining, MTT assay, and flow cytometry were conducted to test cell senescence, proliferation, cell cycle, and apoptosis. PC tissues showed higher expressions of CCNB1 and MDM2 and lower expressions of Bax, caspase-9, caspase-3, and p21. Cells transfected with shCCNB1 had lower expressions of CCNB1 and MDM2, whereas higher expressions of Bax, caspase-9, caspase-3, p53, and p21. The shCCNB1 group had decreased proliferation and S-phase cell proportion and increased apoptosis, senescence, and G0/G1-phase cell proportion. The PFT-alpha group showed higher expressions of MDM2 and lower expressions of Bax, caspase-9, caspase-3, p53, and p21. The PFT-alpha group had increased proliferation and S-phase cell proportion and declined apoptosis, senescence, and G0/G1-phase cell proportion. CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in PC.
引用
收藏
页码:619 / 631
页数:13
相关论文
共 46 条
[21]   Current status and progress of pancreatic cancer in China [J].
Lin, Quan-Jun ;
Yang, Feng ;
Jin, Chen ;
Fu, De-Liang .
WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (26) :7988-8003
[22]   Tumor suppressor p53 and its mutants in cancer metabolism [J].
Liu, Juan ;
Zhang, Cen ;
Hu, Wenwei ;
Feng, Zhaohui .
CANCER LETTERS, 2015, 356 (02) :197-203
[23]   Gene therapy in pancreatic cancer [J].
Liu, Si-Xue ;
Xia, Zhong-Sheng ;
Zhong, Ying-Qiang .
WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (37) :13343-13368
[24]   Non-Cell-Autonomous Tumor Suppression by p53 [J].
Lujambio, Amaia ;
Akkari, Leila ;
Simon, Janelle ;
Grace, Danielle ;
Tschaharganeh, Darjus F. ;
Bolden, Jessica E. ;
Zhao, Zhen ;
Thapar, Vishal ;
Joyce, Johanna A. ;
Krizhanovsky, Valery ;
Lowe, Scott W. .
CELL, 2013, 153 (02) :449-460
[25]  
Mendoza Michael, 2014, Biomol Concepts, V5, P9, DOI 10.1515/bmc-2013-0027
[26]   Pancreatic cancer: Advances in treatment [J].
Mohammed, Somala ;
Van Buren, George, II ;
Fisher, William E. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (28) :9354-9360
[27]   Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer [J].
Morton, Jennifer P. ;
Timpson, Paul ;
Karim, Saadia A. ;
Ridgway, Rachel A. ;
Athineos, Dimitris ;
Doyle, Brendan ;
Jamieson, Nigel B. ;
Oien, Karin A. ;
Lowy, Andrew M. ;
Brunton, Valerie G. ;
Frame, Margaret C. ;
Evans, T. R. Jeffry ;
Sansom, Owen J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (01) :246-251
[28]   Cyclin B1 is a prognostic proliferation marker with a high reproducibility in a population-based lymph node negative breast cancer cohort [J].
Nimeus-Malmstrom, E. ;
Koliadi, A. ;
Ahlin, C. ;
Holmqvist, M. ;
Holmberg, L. ;
Amini, R. -M. ;
Jirstrom, K. ;
Warnberg, F. ;
Blomqvist, C. ;
Ferno, M. ;
Fjallskog, M. -L. .
INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (04) :961-967
[29]  
Pagani Ilaria S, 2014, Oncoscience, V1, P510
[30]   Therapeutic options for the management of pancreatic cancer [J].
Rossi, Maria L. ;
Rehman, Azeem A. ;
Gondi, Christopher S. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (32) :11142-11159