PMID- 29344639
OWN - NLM
STAT- MEDLINE
DCOM- 20180829
LR  - 20240315
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 41
IP  - 4
DP  - 2018 Apr
TI  - Therapeutic potential of a dual mTORC1/2 inhibitor for the prevention of 
      posterior capsule opacification: An in vitro study.
PG  - 2099-2107
LID - 10.3892/ijmm.2018.3398 [doi]
AB  - Mammalian target of rapamycin (mTOR) serves a central role in regulating cell 
      growth and survival, and has been demonstrated to be involved in the pathological 
      progression of posterior capsule opacification (PCO). In the present study, the 
      potency of PP242, a novel dual inhibitor of mTOR complex 1/2 (mTORC1/2), in the 
      suppression of the growth of human lens epithelial cells (HLECs) was 
      investigated. Using a Cell Counting Kit‑8 and a wound healing assay, it was 
      demonstrated that PP242 inhibited the proliferation and migration of HLECs. In 
      addition, western blot analysis indicated that PP242 completely inhibited mTORC1 
      and mTORC2 downstream signaling activities, whereas rapamycin only partially 
      inhibited mTORC1 activity within LECs. Furthermore, PP242 treatment led to an 
      upregulation of the expression levels of p53 and B cell lymphoma‑2 
      (Bcl‑2)‑associated X and downregulation of Bcl‑2. In addition, flow cytometric 
      analysis demonstrated that PP242 induced the cell cycle arrest at the G0/G1 
      phase, which may have caused apoptosis and induced autophagy within the LECs. The 
      results of the present study suggested that administration of PP242 may 
      potentially offer a novel therapeutic approach for the prevention of PCO.
FAU - Feng, Hao
AU  - Feng H
AD  - Department of Ophthalmology, The First Hospital of China Medical University, 
      Shenyang, Liaoning 110001, P.R. China.
FAU - Yang, Zhibo
AU  - Yang Z
AD  - Department of Ophthalmology, The Fourth People's Hospital of Shenyang, Shenyang, 
      Liaoning 110001, P.R. China.
FAU - Bai, Xue
AU  - Bai X
AD  - Department of Ophthalmology, The First Hospital of China Medical University, 
      Shenyang, Liaoning 110001, P.R. China.
FAU - Yang, Meirong
AU  - Yang M
AD  - Department of Ophthalmology, The First Hospital of China Medical University, 
      Shenyang, Liaoning 110001, P.R. China.
FAU - Fang, Yuan
AU  - Fang Y
AD  - Department of Ophthalmology, The First Hospital of China Medical University, 
      Shenyang, Liaoning 110001, P.R. China.
FAU - Zhang, Xiaonan
AU  - Zhang X
AD  - Department of Ophthalmology, The First Hospital of China Medical University, 
      Shenyang, Liaoning 110001, P.R. China.
FAU - Guo, Qiqiang
AU  - Guo Q
AD  - Key Laboratory of Medical Cell Biology, College of Translational Medicine, China 
      Medical University, Shenyang, Liaoning 110001, P.R. China.
FAU - Ning, Hong
AU  - Ning H
AD  - Department of Ophthalmology, The First Hospital of China Medical University, 
      Shenyang, Liaoning 110001, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20180118
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Purines)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - H5669VNZ7V (PP242)
SB  - IM
MH  - Capsule Opacification/metabolism/pathology/*prevention & control
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Enzyme Inhibitors/*pharmacology
MH  - Epithelial Cells/cytology/drug effects/metabolism/pathology
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Lens, Crystalline/cytology/*drug effects/metabolism/pathology
MH  - Mechanistic Target of Rapamycin Complex 1/*antagonists & inhibitors/metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/*antagonists & inhibitors/metabolism
MH  - Purines/*pharmacology
MH  - Signal Transduction/drug effects
PMC - PMC5810205
COIS- Competing interests The authors declare that they have no competing interests.
EDAT- 2018/01/19 06:00
MHDA- 2018/08/30 06:00
PMCR- 2018/01/18
CRDT- 2018/01/19 06:00
PHST- 2017/07/14 00:00 [received]
PHST- 2018/01/10 00:00 [accepted]
PHST- 2018/01/19 06:00 [pubmed]
PHST- 2018/08/30 06:00 [medline]
PHST- 2018/01/19 06:00 [entrez]
PHST- 2018/01/18 00:00 [pmc-release]
AID - ijmm-41-04-2099 [pii]
AID - 10.3892/ijmm.2018.3398 [doi]
PST - ppublish
SO  - Int J Mol Med. 2018 Apr;41(4):2099-2107. doi: 10.3892/ijmm.2018.3398. Epub 2018 
      Jan 18.