【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10d给药RH-0130mg·(kg·d)^-1和60mg·(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30mg·(kg·d)-1和60mg·(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254nm波长,给药12h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