Inhibitory effects of NO-fluvastatin on proliferation of human lens epithelial cells in vitro by modulating cell cycle regulatory proteins.
The effects of NO-Fluvastatin on proliferation of human lens epithelial cells (HLECs) and the action mechanism were investigated. Cell proliferation was assessed by MTT assay. Cell cycle was analyzed by flow cytometry. The expression of cell cycle regulatory proteins CyclinE mRNA and P21(waf1) mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). MTT staining colorimetry showed that HLECs proliferation was markedly inhibited by NO-Fluvastatin and the effect was dependently related to time (24, 48 and 72 h) and dosage (1, 5 and 20 mumol/L). Flow cytometry revealed that NO-Fluvastatin could significantly block HLECs in the G(0)/G(1) phase, resulting in the increased cells in the G(0)/G(1) phase and decreased in the S phase (P<0.05). RT-PCR showed that NO-Fluvastatin could obviously inhibit the CyclinE mRNA expression and induce the P21(waf1) mRNA expression as compared with the negative control groups (P<0.05). This experiment suggested that NO-Fluvastatin could suppress the proliferation of HLECs by regulating cell cycle regulatory proteins (inhibiting the expression of CyclinE mRNA and inducing the expression of P21(waf1) mRNA), resulting in the arrest of HLECs in the G(0)/G(1) phase, which can offer theory basis for NO-Fluvastatin in treating posterior capsular opacification in clinic practice.
Wang
Zhi
Z
Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Hyzhao750@sina.com
Gao
Ruiying
R
Shi
Qianqian
Q
Huang
Yukan
Y
Chen
Wen
W
Shi
Kaiying
K
D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D012333:RNA, Messenger; D000077340:Fluvastatin