RETRACTED: Apatinib Promotes Apoptosis of Pancreatic Cancer Cells through Downregulation of Hypoxia-Inducible Factor-1α and Increased Levels of Reactive Oxygen Species (Retracted Article)

被引:17
作者
He, Ke [1 ,2 ,3 ]
Wu, Lu [4 ,5 ,6 ]
Ding, Qianshan [5 ]
Haider, Farhan [1 ,2 ]
Yu, Honggang [5 ]
Wang, Haihe [1 ,2 ]
Xiang, Guoan [3 ]
机构
[1] Sun Yat Sen Univ, Dept Biochem, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Ctr Stern Cell Biol & Tissue Engn, Key Lab Minist Educ, Guangzhou 510080, Guangdong, Peoples R China
[3] Guangdong Second Prov Gen Hosp, Dept Gen Surg, Guangzhou 510317, Guangdong, Peoples R China
[4] Wuhan Univ, Zhongnan Hosp, Dept Radiat & Med Oncol, Wuhan 430071, Hubei, Peoples R China
[5] Wuhan Univ, Dept Gastroenterol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China
[6] Wuhan Univ, Dept Radiat & Med Oncol, Hubei Key Lab Tumor Biol Behav, Hubei Clin Canc Study Ctr,Zhongnan Hosp, Wuhan 430071, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
TYROSINE KINASE; COLON-CANCER; AUTOPHAGY; INHIBITOR; GROWTH;
D O I
10.1155/2019/5152072
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
At present, apatinib is considered a new generation agent for the treatment of patients with gastric cancer. However, the effects of apatinib on pancreatic cancer have not been clarified. This study investigated the impact of apatinib on the biological function of pancreatic cancer cells and the potential mechanism involved in this process. Using the Cell Counting Kit-8 method, we confirmed that apatinib treatment inhibited cell proliferation in vitro. Moreover, the migration rate of pancreatic cells was inhibited. The effects of apatinib on apoptosis and cell cycle distribution of pancreatic carcinoma cells were detected by flow cytometry. The number of apoptotic cells was significantly increased, and the cell cycle was altered. Furthermore, we demonstrated that apatinib inhibited the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor, and markers of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway, which increased the levels of reactive oxygen species in vitro. Apatinib significantly inhibited the biological function of pancreatic cancer cells. It promoted apoptosis, downregulated the expression of HIF-1 alpha, and increased the levels of reactive oxygen species.
引用
收藏
页数:9
相关论文
共 34 条
[1]   Nanomedicine strategies to overcome the pathophysiological barriers of pancreatic cancer [J].
Adiseshaiah, Pavan P. ;
Crist, Rachael M. ;
Hook, Sara S. ;
McNeil, Scott E. .
NATURE REVIEWS CLINICAL ONCOLOGY, 2016, 13 (12) :750-765
[2]   UPTAKE MICROAUTOPHAGY AND DEGRADATION OF EXOGENOUS PROTEINS BY ISOLATED RAT-LIVER LYSOSOMES - EFFECTS OF PH, ATP, AND INHIBITORS OF PROTEOLYSIS [J].
AHLBERG, J ;
GLAUMANN, H .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 1985, 42 (01) :78-88
[3]   Apatinib - new third-line option for refractory gastric or GEJ cancer [J].
Aoyama, Toru ;
Yoshikawa, Takaki .
NATURE REVIEWS CLINICAL ONCOLOGY, 2016, 13 (05) :268-U21
[4]   Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline [J].
Balaban, Edward P. ;
Mangu, Pamela B. ;
Khorana, Alok A. ;
Shah, Manish A. ;
Mukherjee, Somnath ;
Crane, Christopher H. ;
Javle, Milind M. ;
Eads, Jennifer R. ;
Allen, Peter ;
Ko, Andrew H. ;
Engebretson, Anitra ;
Herman, Joseph M. ;
Strickler, John H. ;
Benson, Al B., III ;
Urba, Susan ;
Yee, Nelson S. .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (22) :2654-U169
[5]   Clinical utility of ramucirumab in advanced gastric cancer [J].
Chan, Matthew M. K. ;
Sjoquist, Katrin M. ;
Zalcberg, John R. .
BIOLOGICS-TARGETS & THERAPY, 2015, 9 :93-105
[6]   Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer [J].
Chatterjee, Sampurna ;
Heukamp, Lukas C. ;
Sioba, Maike ;
Schoettle, Jakob ;
Wieczorek, Caroline ;
Peifer, Martin ;
Frasca, Davide ;
Koker, Mirjam ;
Koenig, Katharina ;
Meder, Lydia ;
Rauh, Daniel ;
Buettner, Reinhard ;
Wolf, Juergen ;
Brekken, Rolf A. ;
Neumaier, Bernd ;
Christofori, Gerhard ;
Thomas, Roman K. ;
Ulrich, Roland T. .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (04) :1732-1740
[7]   An Update on the Current and Emerging Targeted Agents in Metastatic Colorectal Cancer [J].
Chu, Edward .
CLINICAL COLORECTAL CANCER, 2012, 11 (01) :1-13
[8]   Metabolism and Pharmacokinetics of Novel Selective Vascular Endothelial Growth Factor Receptor-2 Inhibitor Apatinib in Humans [J].
Ding, Juefang ;
Chen, Xiaoyan ;
Gao, Zhiwei ;
Dai, Xiaojian ;
Li, Liang ;
Xie, Cen ;
Jiang, Haoyuan ;
Zhang, Lijia ;
Zhong, Dafang .
DRUG METABOLISM AND DISPOSITION, 2013, 41 (06) :1195-1210
[9]   Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study [J].
Ding, Juefang ;
Chen, Xiaoyan ;
Dai, Xiaojian ;
Zhong, Dafang .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2012, 895 :108-115
[10]   Clinical advances in the development of novel VEGFR2 inhibitors [J].
Fontanella, Caterina ;
Ongaro, Elena ;
Bolzonello, Silvia ;
Guardascione, Michela ;
Fasola, Gianpiero ;
Aprile, Giuseppe .
ANNALS OF TRANSLATIONAL MEDICINE, 2014, 2 (12)