Pazopanib inhibits the proliferations of thyroid cancer cells and vascular endothelial cells by cell cycle arrest
Guo Lijuan
Zheng Yan
Liu Pengfei
Wang Entong
Abstract：Objective To investigate the in vitro effects of pazopanib,a tyrosine kinase inhibitor,on the proliferations of both thyroid cancer cells and vascular endothelial cells and underlying mechanisms.Methods The cultured human anaplastic thyroid carcinoma cell line SW579 and human umbilical vein endothelial cell line HUVEC were exposed to pazopanib at different concentrations (1,2,4,8 and 16 μmol/L) for up to 72 hours,and the pazopanib-untreated cells were as control.The effects of pazopanib on the cell proliferations were assessed by cell viability assay,cell imaging analysis and mitosis index measure with immunofluorecent staining of mitosisi cells.Cell cycle analysis was performed by flow cytometry.Results Cell viability assay indicated that pazopanib inhibited the proliferations of both SW579 and HUVEC,in time-and dose-dependent manners,with the estimated IC50 of 2 μmol/L and 4 μmol/L,respectively.Cell imaging analysis showed that pazopanib at IC50 inhibited significantly the growths of SW579 and HUVEC,with significant decreased in the cell densities.Immunofluorecent staining for mitosis cells demonstrated that the mitosis index (0.9％) of the pazopanib-treated SW579 at 48 hours was lower significantly than that (2.2％) of control cells (P ＜ 0.01),and also the mitosis index (1.9％) of pazopanib-treated HUVEC at 48 hours was lower significantly than that of control cells (4.0％) (P ＜ 0.01).Flow cytometry demonstrated that pazopanib induced SW579 cells to arrest at G1 phase.At 24 hours and 48 hours,the percentages of pazopanib-treated SW579 in G1 phase were higher significantly than that of control group cells [(60.4 ± 2.2) ％ vs (49.2 ± 1.6) ％,(70.4 ± 1.6) ％ vs (58.6 ± 3.3) ％] (P ＜ 0.01),while the percentages of pazopanib-treated HUVEC in S phase were higher significantly than that of control group cells [(47.3 ± 2.7) ％ vs (39.5 ±0.6)％,(43.5 ±1.6)％ vs (28.8 ±4.2)％] (P9＜0.01).Conclusions Pazopanib inhibits the proliferations of both SW579 and HUVEC by inducing cell cycle arrest at different phases,leading G1 block of SW579 and S phase arrest of HUVEC respectively.Pazopanib is indicated as a new tyrosine kinase inhibitor to be used for the treatment of thyroid cancer by targeting both tumor cells and vascular endothelial cells related to tumor angiogenesis.
Keywords：PazopanibThyroid carcinoma cell line SW579Vascular endothelial cell line HUVECCell proliferationCell cycle arrest
Publication Date：2014-01-01
Online Publishing Date：2026-09-14(First online date of this platform, not the publication date of the document)
Pages：5( 191-195 )