中国药学杂志
    
           首页  |  期刊介绍  |  编 委 会  |  投稿指南  |  期刊订阅  |  广告服务  |  会议信息  |  联系我们  | 
�й�ҩѧ��־ 2013, Vol. 48 Issue (13) :1069-1075    DOI: 10.11669/cpj.2013.13.008
��Դ����� ����Ŀ¼ | ����Ŀ¼ | ������� | �߼����� << | >>
���ܼ��Ծ����˰�ϸ����Ӱ������
��Ө1,2,����1,���˺�1*,����1,3*
1. �й�ҽѧ��ѧԺ-����Э��ҽѧԺҩ���о���,���� 100050;
2. �����ҽҩ��ѧ,��� 300193; 3. �廪��ѧҽѧԺҩѧϵ,���� 100084
WANG Ying1,2, MA Yao1, CHEN Nai-hong1*, LIU Gang1,3*
1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050,China;
2. Tianjin University of Traditional Chinese Medicine, Tianjin 300193,China;
3. Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084,China

Download: PDF (839KB)   HTML (1KB)   Export: BibTeX or EndNote (RIS)      Supporting Info
ժҪ Ŀ�� ������ҩ��ɸѡ���ø������ܼ������ܼ�������������ܻ������ʵ��ϵͳ�����˸��ೣ�����ܼ���9���˰�ϸ��������Ӱ��,Ϊ�ܽ��ˮ���Կ�����������ѡȡ�ʵ���ý�ṩ�ο������� ���û����޵���B��,�о����Ҷ���400(PEG400)����ɽ������(��ɽ����20����ɽ����80)���Ҵ�����������������ϩ����������(Cremophor EL)�����׻�����ǰ�����ܼ�����׻�����ͬ��ȵĹ�19���ܼ���϶�������ԽϿ��A549(�˷ΰ�ϸ����)��HCT116(�˳���ϸ����)��786-0(������ϸ����)��OVCAR-3(���ѳ���ϸ����)��K562(�˰�Ѫ��ϸ����)��SF295(CNS)��DU-145(��ǰ���ٰ�ϸ����)��MCF7(�����ٰ�ϸ����)��UACC-257(�˺�ɫ����ϸ����)��9���˰�ϸ��������Ӱ�졣��� ϸ��������>90%(percentage growth)ʱ��Ϊ�ܼ���ϸ��������������������;80%<ϸ��������<90%ʱ��Ϊ����������;ϸ��������<80%ʱ��Ϊǿ�������á���ʵ����Ϊ�������������û�����������������(ϸ��������>80%)���ܼ�ϵͳ������ɸѡ�������׻�������������С��0.1%ʱ��9�ֲ���ϸ������ʾ���������û���������������;����PEG400���Ҵ����������Ϊ0.25%�Լ����������������Ϊ0.5%ʱ,��9�ֲ����˰�ϸ��������������; PEG400���Ҵ�������������׻�������Ϊ1��1(�����),�����������Ϊ0.25%ʱ��9���˰�ϸ��������������;PEG400����׻�������Ϊ1��9(�����),���������Ϊ0.1%���Ҵ�������������׻�������Ϊ1��9(�����),���������Ϊ0.25%ʱ�Ծ���ϸ��������Ϊ����������;������ɽ����20����ɽ����80��Cremophor EL�Լ���������׻�������Ϊ1��1(�����)ʱ,���������0.1%�����еIJ��԰�ϸ�������ֳ�������ǿ��������;������Ϊ1��9(�����)ʱ,�����н�Cremophor EL/���׻���������������Ϊ0.1%ʱ��ѡ��������A549��786-0��OVCAR-3��SF295��DU-145��UACC-257��5��ϸ����ɸѡ������ ��������9���˰�ϸ��ɸѡ����������ʱ,�Ҵ�����������PEG400����������׻�����ͬ��������(1��1��1��9)ʱ,�Ƽ�ʹ��������ٷֱȲ�����0.5%(0.25%/0.25%��0.05%/0.45%);�������׻����ʹ���������������0.25%Ϊ��;������ʹ�û���Ӿ�ɽ����20����ɽ����80��Cremophor EL�������ܼ�,����Ҫʱ���ڵͱ�������ܼ�������С��ʹ��Cremophor EL���ܡ���ͬϸ�������жȲ�ͬ,�˰�Ѫ��ϸ��K562�������ܼ���������,�����ٰ�ϸ��MCF7����Զ��׻��������,ʹ��ʱӦ�ر�ע�⡣
Service
�ѱ����Ƽ�������
�����ҵ����
�������ù�����
Email Alert
RSS
�����������
��Ө
����
���˺�*
����
*
�ؼ����� �˰�ϸ��   ������������   ��ˮ���Ի�����   �����޵���B     
Abstract�� Objective 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% final concentration had weak inhibition to all tested tumor cell lines. All Tween 20, Tween 80, Cremophor EL and their mixtures of DMSO at 1��1(V:V) are clearly cytotoxic to all tested cell lines even at the lowest final concentration of 0.1%. It is appreciate that Cremophor EL/DMSO, at 0.1% final concentration with a 1��9 ratio is acceptable for A549(non-small cell lung tumour), 786-0(Renal), OVCAR-3(Ovarian), SF295(CNS), DU-145(Prostate) and UACC-257(Melanoma) cell lines. Conclusion Ethanol, glycerol, PEG400 and their mixtures with DMSO at 1��1(V:V) or 1��9(V:V) are recommended with a final volume percentage of not more than 0.5%; DMSO should be used with a final concentration of less than 0.25%(V:V); Tween 20, Tween 80, Cremophor EL and their mixtures with DMSO are not recommended. It should be noted that the tested cell lines are capable of resisting to the different solvents. As described above, human leukemia cell line K562 is particularly sensitive to all tested solvents, breast tumour cell MCF7 is especially sensitive to DMSO.
Keywords�� human tumor cell,   cytotoxicity,   low water soluble compound,   sulforhodamine B     
�ո�����: 2012-11-27;
��������:

������Ŀ:������Ȼ��ѧ����������Ŀ(81273364)

ͨѶ���� ����,��,�о�Ա �о�������ϻ�ѧ�뻯ѧ����ѧ
Tel/Fax(010)62797740 E-mailgangliu27@tsinghua.edu.cn;���˺�,��,�о�Ա �о�������ϵͳ��������ҩ�↑�������û��� Tel/Fax(010)63165177 E-mailchennh@imm.ac.cn     Email: gangliu27@tsinghua.edu.cn
���߼��: ��Ө,Ů,˶ʿ�о��� �о����������������ɸѡ
���ñ���:   
��Ө, , ������ .���ܼ��Ծ����˰�ϸ����Ӱ������[J]  �й�ҩѧ��־, 2013,V48(13): 1069-1075
WANG Ying-, , MA Yao- etc .Cytotoxicity of Solubilizer on Nine Human Tumor Cell Lines[J]  Chinese Pharmaceutical Journal, 2013,V48(13): 1069-1075
��
[1] SHOEMAKER R H. The NCI60 human tumour cell line anticancer drug screen.Nat Rev Cancer, 2006, 6(10):813-823.
[2] MERISKO L E, LIVERSIDGE G G. Nanosizing for oral and parenteral drug delivery: A perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv Drug Deliv Rev, 2011, 63(3):427-440.
[3] KERNS E H.High throughput physicochemical profiling for drug discovery.J Pharm Sci, 2001, 90(11):1838-1858.
[4] ZAMPIERI S, GHIRARDELLO A, DORIA A, et al. The use of Tween 20 in immunoblotting assays for the detection of autoantibodies in connective tissue diseases. J Immunol Methods, 2000, 239(1-2):1-11.
[5] PATRAVALE V B, DATE A A, KULKARNI R M. Nanosuspensions: A promising drug delivery strategy.J Pharm Pharmacol, 2004, 56(7):827-840.
[6] CHENG X, HOCHLOWSKI J, TANG H, et al. Studies on repository compound stability in DMSO under various conditions. J Biomol Screen, 2003, 8(3):292-304.
[7] BALAKIN K V, IVANENKOV Y A, SKORENKO A V, et al. In silico estimation of DMSO solubility of organic compounds for bioscreening. J Biomol Screen, 2004,9(1):22-31.
[8] GANESAN A. The impact of natural products upon modern drug discovery.Curr Opin Chem Biol, 2008,12(3):306-317.
[9] JOHNSTON P A. Cellular platforms for HTS: Three case studies.Drug Discov Today, 2002,7(6):353-363.
[10] JI S Y, WENG Z Y, ZHOU Y P. The cytotoxicity of some organic solvents in common use on human tumor cell lines .J Yunnan Univ(���ϴ�ѧѧ��:��Ȼ��ѧ��), 2001,23(6):457-460.
[11] SKEHAN P, STORENG R, ACUDIERO D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening.J Natl Cancer Inst, 1990, 82(13):1107-1112.
[12] RANDALL K, CHENG S W, KOTCHEVAR A T. Evaluation of surfactants as solubilizing agents in microsomal metabolism reactions with lipophilic substrates. In Vitro Cell Dev Biol Anim, 2011, 47(9):631-639.
Copyright 2010 by �й�ҩѧ��־