Palbociclib induces cell cycle arrest and senescence of human renal tubular epithelial cells
10.12122/j.issn.1673-4254.2020.12.13
- Author:
Liuwei HUANG
1
;
Yanting SHEN
1
;
Chongbin LIU
1
;
Caizhen LI
1
;
Jun WANG
1
Author Information
1. National Clinical Research Center of Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
- Publication Type:Journal Article
- Keywords:
cell proliferation;
cellular senescence;
palbociclib;
renal tubule epithelial cells
- MeSH:
Cell Cycle;
Cell Cycle Checkpoints;
Cellular Senescence;
Epithelial Cells;
Humans;
Piperazines/pharmacology*;
Pyridines/pharmacology*;
Tumor Suppressor Protein p53/genetics*
- From:
Journal of Southern Medical University
2020;40(12):1784-1792
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of palbociclib on cell cycle progression and proliferation of human renal tubular epithelial cells.
METHODS:Human renal tubular epithelial cell line HK-2 was treated with 1, 5, 10, and 20 μmol/L of palbociclib, and the changes in cell proliferation and viability were examined by cell counting and CCK8 assay. EDU staining was used to assess the proliferation of HK-2 cells following palbiciclib treatment at different concentrations for 5 days. The effect of palbociclib on cell cycle distribution of HK-2 cells was evaluated using flow cytometry. SA-β-Gal staining and C12FDG senescence staining were used to detect senescence phenotypes of HK-2 cells after palbociclib treatment at different concentrations for 5 days. The relative mRNA expression levels of P16, P21, and P53 and the genes associated with senescence-related secretion phenotypes were detected by RT-PCR, and the protein expressions of P16, P21 and P53 were detected by Western blotting.
RESULTS:Palbociclib inhibited HK-2 cell proliferation and induced cell cycle arrest in G1 phase. Compared with the control cells, HK-2 cells treated with high-dose (10 μmol/L) palbociclib exhibited significantly suppressed cell proliferation activity, and the inhibitory effect was the most obvious on day 5 (
CONCLUSIONS:Palbociclib induces HK-2 cell senescence by causing cell growth arrest and delaying cell cycle progression.