PMID- 30219235
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20190528
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 504
IP  - 4
DP  - 2018 Oct 12
TI  - Molecularly targeted anti-cancer drugs inhibit the invasion and metastasis of 
      hepatocellular carcinoma by regulating the expression of MMP and TIMP gene 
      families.
PG  - 878-884
LID - S0006-291X(18)31908-9 [pii]
LID - 10.1016/j.bbrc.2018.08.203 [doi]
AB  - To investigate the effect of multi-kinase kinase inhibitors (sorafenib; 
      regorafenib; lenvatinib) on the invasion and metastasis of human hepatocellular 
      carcinoma (HCC) cells, and the outcome of this effect on the expression of matrix 
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), yet unclarified. 
      Cells were subjected to four different treatments: blank control group, sorafenib 
      (10 mumol/L) treatment group, regorafenib (20 mmol/L) treatment group, and 
      lenvatinib (4 mumol/L) treatment group. Anti-invasion and anti-metastasis effects 
      were tested using the wound-healing assay and transwell invasion assay. Real-time 
      PCR and Western blot analyses were used to determine the impact of sorafenib, 
      regorafenib, and lenvatinib on the gene expression of MMPs and TIMPs in the two 
      HCC lines (Hep3B and SMMC-7721). Results from the wound-healing and transwell 
      invasion assays showed the three tested anti-cancer drugs to have a significant 
      inhibitory effect on the metastasis and invasion of HCC cells. Real-time PCR and 
      western blot analyses revealed that sorafenib down-regulated the expressions of 
      MMP-7,10,16 and up-regulated those of TIMP-1,3,4, regorafenib down-regulated the 
      expression of MMP-1 and up-regulated TIMP-3 gene expression, and lenvatinib 
      down-regulated the expressions of MMP-1,2,7,9,10,16 and up-regulated those of 
      TIMP-1,3,4. However, these three targeted anti-cancer drugs seem to have no 
      significant regulatory effect on the expressions of other MMPs and TIMPs family 
      genes. In conclusion, sorafenib, regorafenib, and lenvatinib inhibit the invasion 
      and metastasis of HCC cells by regulating MMPs/TIMPs expression levels.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - He, Xiao-Xiao
AU  - He XX
AD  - Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Shi, Liang-Liang
AU  - Shi LL
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan, 430022, China.
FAU - Qiu, Meng-Jun
AU  - Qiu MJ
AD  - Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Li, Qiu-Ting
AU  - Li QT
AD  - Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Wang, Meng-Meng
AU  - Wang MM
AD  - Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China.
FAU - Xiong, Zhi-Fan
AU  - Xiong ZF
AD  - Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430077, China. Electronic address: 
      xiongzhifan@126.com.
FAU - Yang, Sheng-Li
AU  - Yang SL
AD  - Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of 
      Science and Technology, Wuhan, 430022, China. Electronic address: 
      yangshengli2014@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20180912
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Quinolines)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 24T2A1DOYB (regorafenib)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EE083865G2 (lenvatinib)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Carcinoma, Hepatocellular/*drug therapy/genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects/genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/genetics/pathology
MH  - Matrix Metalloproteinases/*genetics/metabolism
MH  - Molecular Targeted Therapy/methods
MH  - Multigene Family
MH  - Phenylurea Compounds/pharmacology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Pyridines/pharmacology
MH  - Quinolines/pharmacology
MH  - Sorafenib/pharmacology
MH  - Tissue Inhibitor of Metalloproteinases/*genetics/metabolism
OTO - NOTNLM
OT  - Hepatocellular carcinoma
OT  - Invasion
OT  - Levnatinib
OT  - Metastasis
OT  - Regorafenib
OT  - Sorafenib
EDAT- 2018/09/17 06:00
MHDA- 2019/05/29 06:00
CRDT- 2018/09/17 06:00
PHST- 2018/08/23 00:00 [received]
PHST- 2018/08/31 00:00 [accepted]
PHST- 2018/09/17 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
PHST- 2018/09/17 06:00 [entrez]
AID - S0006-291X(18)31908-9 [pii]
AID - 10.1016/j.bbrc.2018.08.203 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Oct 12;504(4):878-884. doi: 
      10.1016/j.bbrc.2018.08.203. Epub 2018 Sep 12.