黏着斑激酶抑制剂TAE226对人口腔鳞癌细胞增殖的影响
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摘要
目的研究黏着斑激酶抑制剂TAE226对口腔鳞癌HSC-3细胞增殖能力的影响,为临床治疗提供参考。方法 (1)采用CCK-8法检测不同浓度的TAE226(1、5、10、20μmol/L)作用细胞12、24、36、48、60、72h后的光密度(OD)值,计算不同浓度的TAE226在不同时间对该细胞增殖的抑制率;(2)采用流式细胞术检测不同浓度的TAE226对口腔鳞癌细胞周期和凋亡的影响;(3)采用SPSS17.0软件对数据进行统计学分析。结果 (1)CCK-8法增殖实验结果:与对照组相比,不同浓度的TAE226作用于人口腔鳞癌HSC-3细胞株后,均对细胞增殖有抑制作用(P<0.05)。当TAE226的浓度为1、5μmol/L时,在12h时细胞增殖抑制率与对照组比较差异无统计学意义(P>0.05),但是随着时间的延长,差异有统计学意义(P<0.05)。随着TAE226浓度的逐渐升高,其对口腔鳞癌HSC-3细胞增殖的抑制作用逐渐增强(P<0.05)。(2)流式细胞术结果:TAE226可以促进口腔鳞癌细胞的凋亡,且与细胞的浓度呈正相关。TAE226可以将HSC-3细胞周期阻滞于G2期。结论TAE226可以有效地抑制HSC-3细胞增殖,促进细胞的凋亡,阻滞细胞周期于G2期。
Objective To study the effect of adhesion spot kinase inhibitor TAE226 on the proliferation ability of oral squamous cell carcinoma HSC-3 cells to provide reference for clinical treatment.Methods(1)The CCK-8 assay was used to detect the optical density(OD)of HSC-3 cells acted by different concentrations of TAE226(1,5,10,20μmol/L)for 12,24,36,48,60,72 hrespectively.The cell proliferation inhibition rates of different concentrations of TAE226 on the cellular proliferation were calculated;(2)the effect of different concentrations of TAE226 on the cell cycle and apoptosis of oral squamous cell carcinoma was examined by adopting the flow cytometry.(3)The data were analyzed by adopting the SPSS17.0 software.Results(1)The CCK-8 proliferation experiment results showed that compared with the control group,the different concentrations of TAE226 acting on human oral squamous cell carcinoma cell line HSC-3 had the inhibiting effect on cell proliferation(P<0.05).When the concentration of TAE226 was 1μmol/L and 5μmol/L,there was no statistically difference significance in the cellular proliferation inhibiting rate at 12 hcompared with the control group.But with the time extension,the difference was statistically significant(P<0.05).With gradual increase of the TAE226 concentration,its inhibitory effect on oral squamous cell carcinoma HSC-3 cell proliferation was increased gradually(P<0.05).(2)The flow cytometry results showed that TAE226 could promote the apoptosis of oral squamous carcinoma cells,moreover had a positive correlation with the cell concentration.Meanwhile,TAE226 could block the cell cycle at G2 phase.Conclusion TAE226 can effectively inhibit the cell proliferation of HSC-3 cells,promote the cell apoptosis and block the cell cycle in G2 phase.
Objective To study the effect of adhesion spot kinase inhibitor TAE226 on the proliferation ability of oral squamous cell carcinoma HSC-3 cells to provide reference for clinical treatment.Methods(1)The CCK-8 assay was used to detect the optical density(OD)of HSC-3 cells acted by different concentrations of TAE226(1,5,10,20μmol/L)for 12,24,36,48,60,72 hrespectively.The cell proliferation inhibition rates of different concentrations of TAE226 on the cellular proliferation were calculated;(2)the effect of different concentrations of TAE226 on the cell cycle and apoptosis of oral squamous cell carcinoma was examined by adopting the flow cytometry.(3)The data were analyzed by adopting the SPSS17.0 software.Results(1)The CCK-8 proliferation experiment results showed that compared with the control group,the different concentrations of TAE226 acting on human oral squamous cell carcinoma cell line HSC-3 had the inhibiting effect on cell proliferation(P<0.05).When the concentration of TAE226 was 1μmol/L and 5μmol/L,there was no statistically difference significance in the cellular proliferation inhibiting rate at 12 hcompared with the control group.But with the time extension,the difference was statistically significant(P<0.05).With gradual increase of the TAE226 concentration,its inhibitory effect on oral squamous cell carcinoma HSC-3 cell proliferation was increased gradually(P<0.05).(2)The flow cytometry results showed that TAE226 could promote the apoptosis of oral squamous carcinoma cells,moreover had a positive correlation with the cell concentration.Meanwhile,TAE226 could block the cell cycle at G2 phase.Conclusion TAE226 can effectively inhibit the cell proliferation of HSC-3 cells,promote the cell apoptosis and block the cell cycle in G2 phase.
引文
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[6]RAYESS H M,XI Y,GARSHOTT D M,Brownell A L,et al.Benzethonium chloride activates ER stress and reduces proliferation in HNSCC[J].Oral Oncol,2018,76(1):27-33.
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[9]CHANG Y L,HSU Y K,WU T F,et al.Regulation of estrogen receptor alpha function in oral squamous cell carcinoma cells by FAK signaling[J].Endocr Relat Cancer,2014,21(4):555-565.
[10]CHIU Y W,LIOU L Y,CHEN P T,et al.Tyrosine 397phosphorylation is critical for FAK-promoted Rac1activation and invasive properties in oral squamous cell carcinoma cells[J].Lab Invest,2016,96(3):296-306.
[11]陈瑛,王丹丹,朱虹.抗肿瘤新靶点黏着斑激酶FAK及其抑制剂研究进展[J].中国现代应用药学,2016,33(2):255-260.
[12]BEIERLE E A,TRUJILLO A,NAGARAM A,.TAE226inhibits human neuroblastoma cell survival[J].Cancer Invest,2008,26(2):145-151.
[2]WANG Y J,ZHANG Z F,FAN S H,et al.MicroRNA-433inhibits oral squamous cell carcinoma cells by targeting FAK[J].Oncotarget,2017,8(59):100227-100241.
[3]ZHANG D,WU H,ZHANG X,et al.Phosphoglycerate Mutase 1predicts the poor prognosis of oral squamous cell carcinoma and is associated with cell migration[J].JCancer,2017,8(11):1943-1951.
[4]CHI A C,DAY T A,NEVILLE B W.Oral cavity and oropharyn-geal squamous cell carcinoma-an update[J].CA Cancer J Clin,2015,65(5):401-421.
[5]OTANI H,YAMAMOTO H,TAKAOKA M,et al.TAE226,a bis-anilino pyrimidine compound,inhibits the EGFR-mutant kinase including T790M mutant to show anti-tumor effect on EGFR-mutant Non-small cell lung cancer cells[J].PLoS One,2015,10(6):e0129838.
[6]RAYESS H M,XI Y,GARSHOTT D M,Brownell A L,et al.Benzethonium chloride activates ER stress and reduces proliferation in HNSCC[J].Oral Oncol,2018,76(1):27-33.
[7]FERLAY J,SOERJOMATARAM I,DIKSHIT R,et al.Cancer incidence and mortality worldwide:sources,methods and major patterns in GLOBOCAN 2012[J].Int JCancer,2015,136(5):E359-386.
[8]XIA J,LV N,HONG Y,et al.Increased expression of focal adhesion kinase correlates with cellular proliferation and apoptosis during 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis[J].J Oral Pathol Med,2009,38(6):524-529.
[9]CHANG Y L,HSU Y K,WU T F,et al.Regulation of estrogen receptor alpha function in oral squamous cell carcinoma cells by FAK signaling[J].Endocr Relat Cancer,2014,21(4):555-565.
[10]CHIU Y W,LIOU L Y,CHEN P T,et al.Tyrosine 397phosphorylation is critical for FAK-promoted Rac1activation and invasive properties in oral squamous cell carcinoma cells[J].Lab Invest,2016,96(3):296-306.
[11]陈瑛,王丹丹,朱虹.抗肿瘤新靶点黏着斑激酶FAK及其抑制剂研究进展[J].中国现代应用药学,2016,33(2):255-260.
[12]BEIERLE E A,TRUJILLO A,NAGARAM A,.TAE226inhibits human neuroblastoma cell survival[J].Cancer Invest,2008,26(2):145-151.