增溶剂对九类人癌细胞的影响作用  

Cytotoxicity of Solubilizer on Nine Human Tumor Cell Lines

作　　者：王莹[1,2] 马瑶[1] 陈乃宏[1] 刘刚[1,3] 

机构地区：[1]中国医学科学院-北京协和医学院药物研究所,北京100050 [2]天津中医药大学,天津300193 [3]清华大学医学院药学系,北京100084

出　　处：《中国药学杂志》2013年第13期1069-1075,共7页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(81273364)

摘　　要：目的抗肿瘤药物筛选常用各种增溶剂或者溶剂混合物增溶难溶化合物。本实验系统考察了各类常见助溶剂对9类人癌细胞生长的影响,为溶解低水溶性抗肿瘤化合物选取适当溶媒提供参考。方法 采用磺酰罗丹明B法,研究聚乙二醇400(PEG400)、聚山梨酯类(聚山梨酯20、聚山梨酯80)、乙醇、丙三醇、聚氧乙烯环氧蓖麻油(Cremophor EL)、二甲基亚砜及前六种溶剂与二甲基亚砜不同配比的共19种溶剂组合对生长相对较快的A549(人肺癌细胞株)、HCT116(人肠癌细胞株)、786-0(人肾癌细胞株)、OVCAR-3(人卵巢癌细胞株)、K562(人白血病细胞株)、SF295(CNS)、DU-145(人前列腺癌细胞株)、MCF7(人乳腺癌细胞株)及UACC-257(人黑色素瘤细胞株)等9种人癌细胞生长的影响。结果 细胞生长率>90%(percentagegrowth)时视为溶剂对细胞生长无明显抑制作用;80%<细胞生长率<90%时视为弱抑制作用;细胞生长率<80%时视为强抑制作用。本实验认为具有弱抑制作用或者无明显抑制作用(细胞生长率>80%)的溶剂系统可用于筛选。当二甲基亚砜终体积分数小于0.1%时对9种测试细胞均显示弱抑制作用或无明显抑制作用;单独PEG400及乙醇终体积分数为0.25%以及丙三醇终体积分数为0.5%时,对9种测试人癌细胞呈弱抑制作用;PEG400、乙醇及丙三醇与二甲基亚砜比例为1∶1(体积比),在终体积分数为0.25%时对9种人癌细胞呈弱抑制作用;PEG400与二甲基亚砜比例为1∶9(体积比),终体积分数为0.1%、乙醇及丙三醇与二甲基亚砜比例为1∶9(体积比),终体积分数为0.25%时对九种细胞的作用为弱抑制作用;单独聚山梨酯20、聚山梨酯80、Cremophor EL以及三者与二甲基亚砜比例为1∶1(体积比)时,在体积分数0.1%对所有的测试癌细胞均表现出显著的强抑制作用;当比例为1∶9(体积比)时,三者中仅Cremophor EL/二甲基亚砜在终体积分数为0.1%时可选择性用于A549、7Objective To screen anti-tumour compounds in vitro, various solvents may be used to improve the solubility of the insoluble compounds in water. This article analyzes and selects the appropriate solubilizers from 19 single solvent and mixtures of solvents via study their cytotoxicity on typical nine categories of human tumour cell lines, and thus provides a reference for testing those compounds with low-water solubility. Methods Sulforhodamine B （SRB） assay was performed on human tumor cells inhibition including A549（non-small cell lung）, HCT116（Colon）, 786-0（Renal）, OVCAR-3（Ovarian）, K562（Leukemia）, SF295（CNS）, DU-145（Prostate）, MCF7（Breast） and UACC-257（Melanoma）. Nineteen single or mixtures of solvents were investigated including PEG400, Tween 20, Tween 80, ethanol, glycerol, Cremophor EL, DMSO and the twelve mixtures with DMSO in the proportions of 1∶1（V∶V） and 1∶9（V∶V）. Results When the cell percentage growth is greater than 90%, it is deemed as that this solvent had no inhibitory effect on cell growth. When the cell percentage growth is between 80% and 90%, it is considered as a weak inhibition. When cell percentage growth is less than 80%, it is defined as strong inhibition solvent. Furthermore, weak or no inhibition of the solvent system is recommended for the purpose of high throughput screening of compounds against human tumor cell lines. In this study, we found that final DMSO volume fraction at 0.1%（V∶V） had weak or no inhibition to all tested cell lines. Beyond that, PEG400 and ethanol at final concentration of 0.25%（V∶V）, glycerol at final concentration of 0.5%（V/V） had weak inhibition to all tested cell lines. PEG400, ethanol and glycerol mixed with DMSO with a 1∶1（V/V） ratio had weak inhibition to all tested cell lines at final concentration of 0.25%（V∶V）. However, PEG400 and DMSO mixture（1∶9=V∶V） at final concentration of 0.1%（V∶V）, ethanol and glycerol mixed with DMSO with a 1∶9 ratio at 0.25% fina

关 键 词：人癌细胞 生长抑制作用 低水溶性化合物 磺酰罗丹明B 

分 类 号：R965[医药卫生—药理学]