细胞运动抑制剂4-甲基-3-硝基-苯甲酸的基础研究  

Basic Research of Cell Migration Inhibitor 4-methyl-3-nitro-benzoic Acid

作　　者：李萌辉[1] 张飞[1] 郭华[1] 张晓方[1] 赵陪起[1] 张宁[2] 牛瑞芳[1] 

机构地区：[1]乳腺癌防治教育部重点实验室,天津市肿瘤防治重点实验室,天津医科大学附属肿瘤医院肿瘤研究所,天津市300060 [2]天津医科大学,天津市基础医学研究中心

出　　处：《中国肿瘤临床》2010年第11期601-604,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金资助(编号:30772529)~~

摘　　要：目的:检测小分子化合物4-甲基-3-硝基-苯甲酸的药物毒性作用、对多种恶性肿瘤细胞运动能力的影响以及在小鼠体内对肿瘤生长的抑制作用。方法:将4-甲基-3-硝基-苯甲酸给药剂量按等比数列排列,从而测定它在小鼠体内的半数致死量;体外采用趋化实验检测4-甲基-3-硝基-苯甲酸对肺癌细胞A549、肝癌细胞SSMC-7721、恶性黑色素瘤细胞LiBr及胃癌细胞MGC-803趋化运动能力的影响;体内实验,将BL6-B16细胞接种到C57小鼠,经灌胃给药后,观察4-甲基-3-硝基-苯甲酸对小鼠移植瘤生长的影响,并以生理盐水作对照,同时以体重变化为指标衡量4-甲基-3-硝基-苯甲酸的毒性作用。结果:4-甲基-3-硝基-苯甲酸在小鼠体内的半数致死量LD50为771.73mg/kg;趋化实验表明4-甲基-3-硝基-苯甲酸对多种肿瘤细胞的细胞运动都有明显的抑制作用,并且最适浓度为2.0μM;4-甲基-3-硝基-苯甲酸抑制小鼠黑色素移植瘤生长,肿瘤体积(P<0.05)和重量(P<0.01)显著低于对照组,4-甲基-3-硝基-苯甲酸对小鼠体重变化无影响。结论:4-甲基-3-硝基苯甲酸有望成为治疗恶性肿瘤的新药。Objective： To investigate the effects of the micro-molecular compound 4-methyl-3-nitro-benzoic acid on drug toxicity, migration capacity of various malignant tumor cells and inhibition of tumor growth on mice. Methods： The dosage of 4-methyl-3-nitro-benzoic acid was arranged by geometric series, and then the half lethal dose was measured on mice in vivo. Chemotaxis assay was performed to detect the effects of 4-methyl-3-nitro-benzoic acid on cell migration capacity of the lung cancer cells A549, liver cancer cells SSMC-7721, malignant melanoma cells LiBr and gastric cancer cells MGC-803 in vitro. In vivo, BL6-B16 cells were injected to C57 mice with normal sodium as the control. The effects of 4-methyl-3-nitro-benzoic acid on the growth of the mouse-transplanted tumors were observed after intra-gastric administration. The body weight of the mice was recorded as another measure to estimate the toxic effect of the drug, 4-methyl-3-nitro-benzoic acid. Results： It was shown by acute toxicity testing that the half lethal dose （LD50） of 4-methyl-3-nitro-benzoic acid in mice in vivo is 771.73 mg/kg. Chemotaxis assay showed that 4-methyl-3-nitro-benzoic acid could overtly and markedly inhibit the cell migration of many tumor cells with 2.0 μM as the optimal inhibiting concentration. 4-methyl-3-nitro-benzoic acid could inhibit the growth of mouse-transplanted melanoma, and the tumor volume （P〈0.05） and tumor weight （P〈 0.01） was markedly lower compared to the control group. 4-methyl-3-nitro-benzoic acid demonstrated no effect on body weight change in mice. Conclusions： 4-methyl-3-nitro-benzoic acid promises to be an effective new drug used in the treatment of malignant tumors.

关 键 词：恶性肿瘤 细胞运动 肿瘤抑制 肿瘤治疗 

分 类 号：R96[医药卫生—药理学]