摘要
目的研究缬草酸对结直肠癌HCT116细胞生物学行为的影响及机制。方法将结直肠癌HCT116细胞分为5组:正常培养组、缬草酸低剂量组、缬草酸中剂量组、缬草酸高剂量组、Notch通路抑制剂组(GSI-IX组)。通过5-乙炔基-2’-脱氧尿嘧啶核苷染色实验分析HCT116细胞的增殖能力;通过Transwell实验分析HCT116细胞的侵袭能力;通过细胞划痕实验分析HCT116细胞的迁移能力;通过流式细胞术分析HCT116细胞的凋亡率;通过蛋白免疫印迹实验检测HCT116细胞中跨膜受体蛋白1(Notch1)、HES家族发状分裂相关增强子1(HES1)及HEY家族发状分裂相关增强子1(HEY1)的表达水平。结果各缬草酸剂量组与GSI-IX组结直肠癌HCT116细胞的增殖能力[(16.53±1.29)%、(13.16±2.15)%、(5.61±0.58)%、(6.73±0.75)%]、侵袭数量[(82.26±2.53)个、(68.37±3.79)个、(31.53±2.18)个、(36.75±3.55)个]及迁移率[(62.18±3.75)%、(53.87±3.65)%、(23.15±3.57)%、(28.16±2.62)%]均低于正常培养组[(39.25±2.82)%、(96.27±3.15)个、(82.68±4.66)%],差异有统计学意义(F=367.851、497.388、265.160,均P<0.001)。各缬草酸剂量组与GSI-IX组结直肠癌HCT116细胞的凋亡率[(5.32±0.09)%、(11.05±0.62)%、(15.39±1.25)%、(14.68±1.36)%]高于正常培养组[(2.01±0.08)%],差异有统计学意义(F=270.242,P<0.05)。各缬草酸剂量组与GSI-IX组结直肠癌HCT116细胞的Notch1表达水平(0.63±0.07、0.43±0.06、0.31±0.02、0.28±0.05)、HES1表达水平(0.72±0.07、0.50±0.08、0.33±0.02、0.27±0.03)及HEY1表达水平(0.68±0.05、0.52±0.06、0.37±0.05、0.31±0.07)低于正常培养组(0.79±0.05、0.81±0.05、0.85±0.09),差异有统计学意义(F=102.345、110.722、68.653,均P<0.05)。结论缬草酸能抑制结直肠癌HCT116细胞的增殖、迁移及侵袭,并促进HCT116细胞凋亡,这些作用与调控Notch信号通路有关。
Objective To investigate the effect of valeric acid on the biological behaviors of colorectal cancer HCT116 cells and its underlying mechanism.Methods The colorectal cancer HCT116 cells were divided into five groups:normal culture group,low-dose valeric acid group,medium-dose valeric acid group,high-dose valeric acid group,and Notch pathway inhibitor group(GSI-IX group).The proliferative capacity of HCT116 cells was analyzed by 5-ethynyl-2’-deoxyuridine(EdU)staining.The invasive capacity of HCT116 cells was analyzed by Transwell assay.The migratory capacity of HCT116 cells was analyzed by cell scratch wound healing assay.The apoptosis rate of HCT116 cells was analyzed by flow cytometry.The expression levels of neurogenic locus homolog protein 1(Notch1),hairy and enhancer of split-1(HES1),and hairy/enhancer-of-split related with YRPW motif protein 1(HEY1)in HCT116 cells were detected by Western blotting.Results The proliferative capacity of HCT116 cells in all valeric acid dose groups and the GSI-IX group((16.53±1.29)%,(13.16±2.15)%,(5.61±0.58)%,(6.73±0.75)%),invasive capacity((82.26±2.53)cells,(68.37±3.79)cells,(31.53±2.18)cells,(36.75±3.55)cells)and migratory capacity((62.18±3.75)%,(53.87±3.65)%,(23.15±3.57)%,(28.16±2.62)%)were all lower than those in the normal culture group((39.25±2.82)%,(96.27±3.15)cells,(82.68±4.66)%),and the differences were statistically significant(F=367.851,497.388,265.160,all P<0.001).The apoptosis rate of HCT116 cells in all valeric acid dose groups and the GSI-IX group((5.32±0.09)%,(11.05±0.62)%,(15.39±1.25)%,(14.68±1.36)%)were higher than that in the normal culture group((2.01±0.08)%),and the difference was statistically significant(F=270.242,P<0.05).The expression levels of Notch1(0.63±0.07,0.43±0.06,0.31±0.02,0.28±0.05),HES1(0.72±0.07,0.50±0.08,0.33±0.02,0.27±0.03)and HEY1(0.68±0.05,0.52±0.06,0.37±0.05,0.31±0.07)in HCT116 cells in all valeric acid dose groups and the GSI-IX group were all lower than those in the normal culture group(0.79±0.05,0.81±0.05,0.85±0.09),and the differences were statistically significant(F=102.345,110.722,68.653,all P<0.05).Conclusion Valeric acid can inhibit the proliferation,migration,and invasion of colorectal cancer HCT116 cells,and promote the apoptosis of HCT116 cells.These effects of valeric acid on HCT116 cells is related to the regulation of the Notch signaling pathway.
作者
曹梦颖
晋齐中
邓旭
韩亮
修丽娟
CAO Mengying;JIN Qizhong;DENG Xu;HAN Liang;XIU Lijuan(Department of Pharmacy,Xuzhou Central Hospital,Xuzhou 221009,China;Department of Oncology,Xuzhou Central Hospital,Xuzhou 221009,China)
出处
《中国药物应用与监测》
2025年第9期1604-1608,共5页
Chinese Journal of Drug Application and Monitoring
基金
江苏省科技项目基础研究计划自然科学基金面上项目(BK20231156)
徐州市重点研发计划(社会发展)项目医药卫生面上项目(KC22178)
徐州市药学会-彭城药学科研项目(JL07)。
关键词
缬草酸
结直肠癌
NOTCH信号通路
增殖
迁移
凋亡
侵袭
valeric acid
colorectal cancer
Notch signaling pathway
proliferation
migration
apoptosis
invasion
