Format

Send to

Choose Destination
Int J Mol Med. 2018 Apr;41(4):2099-2107. doi: 10.3892/ijmm.2018.3398. Epub 2018 Jan 18.

Therapeutic potential of a dual mTORC1/2 inhibitor for the prevention of posterior capsule opacification: An in vitro study.

Author information

1
Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
2
Department of Ophthalmology, The Fourth People's Hospital of Shenyang, Shenyang, Liaoning 110001, P.R. China.
3
Key Laboratory of Medical Cell Biology, College of Translational Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China.

Abstract

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.

PMID:
29344639
PMCID:
PMC5810205
DOI:
10.3892/ijmm.2018.3398
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Spandidos Publications Icon for PubMed Central
Loading ...
Support Center