首页|帕比司他靶向ARL4C抑制肾癌细胞增殖、迁移和侵袭的研究

帕比司他靶向ARL4C抑制肾癌细胞增殖、迁移和侵袭的研究

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目的 探讨帕比司他通过靶向ADP核糖基化因子样蛋白4C(ARL4C)对肾癌细胞增殖、迁移和侵袭的影响.方法 将肾癌细胞株786-O分为空白组(用磷酸盐缓冲溶液干预)、实验组(用50 nmol·L帕比司他干预)、空载体组(先转染空载体,然后用磷酸盐缓冲溶液干预)、过表达组(先转染ARL4C过表达载体,然后用磷酸盐缓冲溶液干预)、联合组(先转染ARL4C过表达载体,然后用50 nmol·L-1帕比司他干预).用噻唑蓝法和划痕实验检测细胞的增殖、迁移和侵袭水平,用酶标仪检测细胞内胆固醇水平,用实时荧光定量聚合酶链反应和蛋白质印迹法检测ARL4C mRNA和蛋白的表达水平.结果 空白组、实验组、空载体组、过表达组和联合组的细胞增殖率分别为(100.00±0)%、(61.08±5.82)%、(101.22±5.92)%、(121.94±6.63)%和(101.78±6.87)%,迁移率分别为(44.59±2.49)%、(29.02±2.09)%、(42.75±2.42)%、(54.19±3.05)%和(41.91±2.75)%,侵袭能力分别为(264.50±6.52)、(182.70±5.83)、(257.80±7.91)、(322.40±8.27)和(266.80±8.15)个,胆固醇水平分别为(72.48±6.21)、(36.48±3.44)、(73.89±5.91)、(89.21±8.89)和(73.06±6.92)mmol·L-1,ARL4C mRNA 相对表达水平分别为 1.23±0.22、0.24±0.08、1.27±0.25、1.67±0.38 和 1.27±0.25,ARL4C 蛋白相对表达水平分别为 1.06±0.03、0.17±0.04、1.03±0.05、1.37±0.18 和 1.05±0.08.实验组的上述指标和空白组比较,过表达组的上述指标与空白组和空载体组比较,在统计学上差异均有统计学意义(均P<0.05).结论 帕比司他通过下调ARL4C表达,降低细胞内胆固醇水平,从而抑制肾癌细胞的增殖、迁移和侵袭水平.
Inhibition of proliferation,migration and invasion of renal carcinoma cells by targeting ARL4C with panobinostat
Objective To explore the effects of panobinostat on the proliferation,migration and invasion of renal carcinoma cells via targeting ADP ribosylated factor-like protein 4C(ARL4C).Methods According to different treatments,human renal carinoma 786-O cells were divided into blank group(phosphate buffer treatment),experimental group(50 nmol·L-1 panobinostat treatment),empty vector group(transfection with empty vector and no treatment),overexpression group(transfection with ARL4C overexpression vector and no treatment)and combined group(transfection with ARL4C overexpression vector and 50 nmol·L-1 panobinostat treatment).The proliferation,migration and invasion of cells were detected by methyl thiazolyl tetrazolium assay and scratch assay.Cholesterol transport levels in cells were detected by enzyme-labeled assay.The mRNA and protein levels of ARL4C in cells were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot.Results The indicators of cell proliferation in blank group,experimental group,empty vector group,overexpression group and combined group were(100.00±0)%,(61.08±5.82)%,(101.22±5.92)%,(121.94±6.63)%and(101.78±6.87)%;the indicators of cell migration were(44.59±2.49)%,(29.02±2.09)%,(42.75±2.42)%,(54.19±3.05)%and(41.91±2.75)%;the indicators of cell invasion were 264.50±6.52,182.70±5.83,257.80±7.91,322.40±8.27 and 266.80±8.15;the intracellular levels of cholesterol were(72.48±6.21),(36.48±3.44),(73.89±5.91),(89.21±8.89)and(73.06±6.92)mmol·L-1;the relative expression levels of ARL4C mRNA were 1.23±0.22,0.24±0.08,1.27±0.25,1.67±0.38 and 1.27±0.25;the relative expression levels of ARL4C protein were 1.06±0.03,0.17±0.04,1.03±0.05,1.37±0.18 and 1.05±0.08,respectively.Between the blank group and experimental group,the above indicators have statistically significant differences(all P<0.05);compared with the blank group and empty vector group,the above indicators in overexpression group have statistically significant differences(all P<0.05).Conclusion Panobinostat downregulate the intracellular levels of cholesterol by reducing the expression level of ARL4C in 786-O cells,thus inhibiting the proliferation,migration and invasion of renal carcinoma cells.

panobinostatADP ribosylation like factor 4Crenal cancercell proliferationcholesterol

杨志云、王雪莉、田秀岭

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商丘医学高等专科学校临床医学院,河南商丘 476000

商丘市中心医院肿瘤科,河南商丘 476002

帕比司他 ADP核糖基化因子样蛋白4C 肾癌 细胞增殖 胆固醇

河南省科技攻关指导基金

232102310516

2024

中国临床药理学杂志
中国药学会

中国临床药理学杂志

CSTPCD北大核心
影响因子:1.91
ISSN:1001-6821
年,卷(期):2024.40(11)
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