苯并[a]芘恶性转化16HBE细胞元素组分析及铜与顺铂或长春瑞滨联用对细胞增殖的作用OACSTPCD
Element profiles of benzo[a]pyrene malignantly transformed 16HBE cells and joint effects of copper with cisplatin or vinorelbine on cell proliferation
目的 研究苯并[a]芘(BaP)致细胞恶性转化中元素组的变化,探讨铜与顺铂或长春瑞滨联用对细胞增殖的影响.方法 以16HBE细胞和BaP恶性转化细胞T-16HBE-C1细胞为研究对象,采用电感耦合等离子质谱分析44种元素在2种细胞中的含量,采用偏最小二乘回归分析元素含量对2种细胞的区分能力,采用MTT法检测铜(0,237,340,487,1000和1432 μmol·L-1)、顺铂(0,4.4,6.1,8.6,12.0和16.8 μmol·L-1)和长春瑞滨(0,3.8,9.8,25.0,40.0和64.0 μmol·L-1)对2种细胞存活率的影响,计算半数抑制浓度(IC50).根据IC50比例制备铜与顺铂混合物和铜与长春瑞滨混合物,采用MTT法检测其对细胞存活率的影响,并采用等效线图法分析铜与顺铂或长春瑞滨的联合作用.采用MTT法检测铜(0,50,100,200,400 和800 μmol·L-1)与IC50的顺铂或长春瑞滨联用对T-16HBE-C1细胞存活率的影响.结果 在2种细胞中共检出29种元素,其中铜、锌、银、硒和铷含量在T-16HBE-C1细胞中较16HBE细胞降低(P<0.01,P<0.05),钼、砷、锂、锗、锶、镍、镧、汞、铁和铯含量升高(P<0.01,P<0.05).元素含量可用于区分16HBE和T-16HBE-C1细胞.铜可抑制16HBE和T-16HBE-C1细胞增殖,IC50分别为(613±16)μmol·L-1和(776±15)μmol·L-1(P<0.01).铜与顺铂混合物(1∶69.5)和铜与长春瑞滨混合物(1∶33.4)抑制T-16HBE-C1细胞增殖,且铜与顺铂和长春瑞滨具有相加作用.与单独IC50浓度的顺铂(11.2 μmol·L-1)或长春瑞滨(23.2 μmol·L-1)相比,当铜>400 μmol·L-1,其与IC50浓度的顺铂或长春瑞滨联合作用可抑制T-16HBE-C1细胞增殖.结论 16HBE细胞经BaP恶性转化后元素含量和相关关系发生改变.铜可抑制T-16HBE-C1细胞增殖,且在高浓度时与顺铂和长春瑞滨具有相加的联合作用.
OBJECTIVE To assess the profiles of elements in benzo[a]pyrene(BaP)induced carci-nogenesis,and explore the joint effects of copper with cisplatin or vinorelbine on cell proliferation.METHODS Forty-four elements were measured using an inductively coupled plasma mass spectrometer in 16HBE cells and BaP malignantly transformed 16HBE(T-16HBE-C1)cells.Partial least square was used to validate the robustness of cell classification of elements.Cell viability was measured by MTT assay for copper(0,237,340,487,1000 and 1432 μmol·L-1),cisplatin(0,4.4,6.1,8.6,12.0 and 16.8 μmol·L-1),and vinorelbine(0,3.8,9.8,25.0,40.0 and 64.0 μmol·L-1)to acquire their half maximal inhibitory concentra-tion(IC50).Mixtures of copper and chemotherapeutics were prepared according to the ratio of each IC50.Their joint effects on cell viability were assessed by MTT assay and isobolographic analysis.Inhibition effect of copper(0,50,100,200,400 and 800 μmol·L-1)with IC50 of cisplatin or vinorelbine on prolifera-tion of T-16HBE-C1 cells was also assessed.RESULTS A total of 29 elements were quantified in 16HBE and T-16HBE-C1 cells,among which concentrations of copper,zinc,silver,selenium and rubidium decreased(P<0.05,P<0.01),while those of molybdenum,arsenic,lithium,germanium,strontium,nickel,lanthanum,mercury,iron,and cesium increased(P<0.05,P<0.01)in T-16HBE-C1 cells.Element concen-tration could be used to distinguish T-16HBE-C1 cells from 16HBE cells.Copper concentration-dependently inhibited proliferation of both cells,with a statistically significant lower IC50 of(613±16)μmol·L-1 in 16HBE cells than(776±15)μmol·L-1 in T-16HBE-C1 cells(P<0.01).Mixtures of copper and cisplatin(1∶69.5)or vinorelbine(1∶33.4)could inhibit cell proliferation,and copper had additive effects with cisplatin or vinorelbine.When copper concentration was higher than 400 μmol·L-1,copper combined with IC50 of cisplatin or vinorelbine inhibited cell proliferation of T-16HBE-C1 cells compared with IC50 of cisplatin(11.2 μmol·L-1)or vinorelbine(23.2 μmol·L-1)alone.CONCLUSION Element profiles and correlations can change significantly after 16HBE cells are malignantly transformed by BaP.Copper could inhibit the proliferation of T-16HBE-C1 cells and have additive effects with cisplatin or vinorelbine in higher concentration.
王裕;闫赖赖;付娟玲;郝明媚;陈雯;姚碧云;常兵;赵鹏
北京大学公共卫生学院毒理学系,食品安全毒理学研究与评价北京市重点实验室, 北京 100191||中国疾病预防控制中心环境与健康相关产品安全所,中国疾病预防控制中心环境与人群健康重点实验室,北京 100021北京大学公共卫生学院卫生检验学系,北京 100191北京大学公共卫生学院毒理学系,食品安全毒理学研究与评价北京市重点实验室, 北京 100191中山大学公共卫生学院毒理学系,广东 广州 510080中国疾病预防控制中心职业卫生与中毒控制所,北京 100050
药学
元素组铜顺铂长春瑞滨苯并[a]芘细胞增殖T-16HBE-C1细胞
elementcoppercisplatinvinorelbinebenzo[a]pyrenecell proliferationT-16HBE-C1 cells
《中国药理学与毒理学杂志》 2024 (001)
基于细胞应激反应途径组合测试和毒物基因组学预测化学物肝、肾靶器官毒性
1-10 / 10
National Natural Science Foundation of China(81370079);National Natural Science Foundation of China(81001253);and Beijing Natural Science Foundation(7132122) 国家自然科学基金(81370079);国家自然科学基金(81001253);北京市自然科学基金(7132122)
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