PMID- 25738322
OWN - NLM
STAT- MEDLINE
DCOM- 20151215
LR  - 20220321
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 33
IP  - 5
DP  - 2015 May
TI  - MCM2 is a therapeutic target of lovastatin in human non-small cell lung 
      carcinomas.
PG  - 2599-605
LID - 10.3892/or.2015.3822 [doi]
AB  - Human non-small cell lung carcinoma (NSCLC) is one of the most common cancer 
      worldwide. In previous studies, lovastatin, acting as an inhibitor of 
      3-hydroxy-3-methylglutaryl Co A (HMG-CoA) reductase, exhibited significant 
      antitumor activity during tumorigenesis. However, whether or not this effect is 
      mediated through changes in minichromosome maintenance (MCM) 2 expression remains 
      unclear. The present study investigated whether lovastatin inhibits proliferation 
      due to MCM2 in NSCLCs. We first assessed the effects of lovastatin on cell 
      anti-proliferation, cell cycle progression and apoptosis in NSCLC cells. We 
      found, by quantitative RT-PCR and western blot analysis, that lovastatin 
      treatment markedly and consistently inhibited the expression of MCM2. Then, to 
      further explore the anticancer mechanism of lovastatin involving MCM2, we 
      silenced MCM2 by siRNA in two cell lines (A549 and GLC-82). Silencing of MCM2 
      triggered G1/S arrest. Following further examination of cell cycle-related 
      factors, MCM2 knockdown inhibited protein retinoblastoma (Rb), cyclin D1 and CDK4 
      expression, but increased p21 and p53 expression, suggesting that siMCM2 indeed 
      triggered cell cycle arrest. In addition, siMCM2 induced apoptosis. Finally, 
      lovastatin treatment increased p-JNK, which is involved in the downregulation of 
      MCM2. In conclusion, our data suggest that MCM2 may be a novel therapeutic target 
      of lovastatin treatment in NSCLCs.
FAU - Zhang, Xu
AU  - Zhang X
AD  - Department of Stomatology, The Fourth Affiliated Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, P.R. China.
FAU - Teng, Yang
AU  - Teng Y
AD  - The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 
      Heilongjiang, P.R. China.
FAU - Yang, Fang
AU  - Yang F
AD  - Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, P.R. China.
FAU - Wang, Meng
AU  - Wang M
AD  - Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, P.R. China.
FAU - Hong, Xuan
AU  - Hong X
AD  - Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, P.R. China.
FAU - Ye, Lei-Guang
AU  - Ye LG
AD  - Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, P.R. China.
FAU - Gao, Yi-Na
AU  - Gao YN
AD  - Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, P.R. China.
FAU - Chen, Gong-Yan
AU  - Chen GY
AD  - Department of Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical 
      University, Harbin, Heilongjiang, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150227
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (CCND1 protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 136601-57-5 (Cyclin D1)
RN  - 9LHU78OQFD (Lovastatin)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 3.6.4.12 (MCM2 protein, human)
RN  - EC 3.6.4.12 (Minichromosome Maintenance Complex Component 2)
SB  - IM
MH  - Apoptosis/drug effects/genetics
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics
MH  - Cell Cycle Checkpoints/drug effects/genetics
MH  - Cell Cycle Proteins/genetics
MH  - Cell Line, Tumor
MH  - Cyclin D1/genetics
MH  - Cyclin-Dependent Kinase 4/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p21/genetics
MH  - G1 Phase Cell Cycle Checkpoints/drug effects/genetics
MH  - Humans
MH  - Lovastatin/*pharmacology
MH  - Lung Neoplasms/*drug therapy/*genetics
MH  - MAP Kinase Signaling System/drug effects/genetics
MH  - Minichromosome Maintenance Complex Component 2/*genetics
MH  - Retinoblastoma Protein/genetics
MH  - Tumor Suppressor Protein p53/genetics
EDAT- 2015/03/05 06:00
MHDA- 2015/12/17 06:00
CRDT- 2015/03/05 06:00
PHST- 2014/11/01 00:00 [received]
PHST- 2015/02/02 00:00 [accepted]
PHST- 2015/03/05 06:00 [entrez]
PHST- 2015/03/05 06:00 [pubmed]
PHST- 2015/12/17 06:00 [medline]
AID - 10.3892/or.2015.3822 [doi]
PST - ppublish
SO  - Oncol Rep. 2015 May;33(5):2599-605. doi: 10.3892/or.2015.3822. Epub 2015 Feb 27.