大黄酸衍生物RH-01抑制骨肉瘤生长作用研究  

Effect of rhein derivative RH-01 on the growth of osteosarcoma

作　　者：万宗明[1] 陈虹[2] 谢文利[1] 王莹[2] 晋玉章[1] 

机构地区：[1]武警医学院药理学教研室,天津300162 [2]武警医学院生药学教研室,天津300162

出　　处：《武警医学院学报》2008年第6期469-472,共4页Acta Academiae Medicinae CPAPF

基　　金：国家自然科学基金资助项目(30371682)

摘　　要：【目的】研究大黄酸衍生物RH-01抑制骨肉瘤生长及其骨亲和性的作用。【方法】体外用MTT法对RH-01的活性进行筛选;昆明鼠荷S180肉瘤,连续10 d给药RH-0 130 mg.(kg.d)-1和60 mg.(kg.d)-1,处死动物,称量肿瘤,分析RH-01对体内肿瘤生长的抑制作用;采用体外羟基磷灰石吸附实验测定RH-01的骨亲和性;用紫外分光光度仪测定RH-01在体内的骨亲和性。【结果】经RH-01处理过的人源骨肉瘤HOS细胞,IC50为0.18μmol/L;浓度为30 mg.(kg.d)-1和60 mg.(kg.d)-1两个实验组,RH-01对昆明鼠荷S180肉瘤的生长抑制率分别为64.54%和77.26%;RH-01在体外的骨亲和性明显,羟基磷灰石吸附值为14.8μmol/g,而四环素的吸附值仅为8.1μmol/g;紫外分光光度仪测定结果显示,RH-01在骨内与鬼臼毒素具有相似的光谱图,并且测得在254 nm波长,给药12 h后,经RH-01转运至骨内的鬼臼毒素含量为(5.39±0.03)μg/mg,而对照组的鬼臼毒素的含量为(3.29±0.03)μg/mg。【结论】RH-01体外抑制骨肉瘤HOS细胞生长作用明显,体内也能显著抑制S180肉瘤的生长,而且RH-01在体内外的骨亲和性作用明显。[Objective] To study the effects of rhein derivative RH-01 on the osteosarcoma （HOS） cells. [Methods] HOS cells were treated with RH-01 at different concentrations. The growth inhibition of HOS cells was analyzed by MTT assay. The effect of RH-01 on tumor growth was studied by kunming mice transplanted models with entity-type S180 carneus. Hydroxyapatite ceramic absorption assay and ultraviolet spectrophotometry was employed to analyzed the bone- affinity effect of RH-01 in vitro and vivo respectively. [Results] RH-01 remarkably inhibiteds the growth of HOS cells, the IC50 value was 0.18 μmol/L. After ten days of administering RH-0 130 mg·（kg·d）-1and 60 mg·（kg·d）-1, theS180 carneus in average group was dramatically lighter than the one in negative control group, with inhibition rate of 64.54% and 77.26% respectively. The result of hydroxyapatite ceramic absorbing assay showed that its values towards ACM and RH-01 were 8.1 μmol/g and 14.8 μmol/g respectively. And that the RH-01＇ s spectrogram in bone surveyed by ultraviolet spectrophotometry was the same as Podophyllotoxin , it showed that at the wavelengths of 254 nm, the contents of RH-01 inside bone turned out to be （5.39 ± 0.03） μg/mg after 12 hours, while the contents of Podophyllotoxin being （3.29 ± 0.03） μg/mg. [Conclusions] The compound RH-01 could obviously inhibit the growth of HOS cell line in vitro and S180 carneus in vivo. It also has a very strong bone-affinity feature in vitro and vivo

关 键 词：大黄酸衍生物 骨肉瘤 骨亲和性 生长抑制 

分 类 号：R286.1[医药卫生—中药学]