齐墩果酸类衍生化合物抑制骨肉瘤活性的实验研究

The inhibitive effect of oleanolic acid derivative compounds on the activity of osteosarcoma

目的筛选并验证齐墩果酸(OA)类衍生化合物对骨肉瘤抑制活性,为寻找治疗骨肉瘤的新药提供依据。方法 MTT法筛选并检测OA类化合物对骨肉瘤细胞增殖活性的影响,Annexin V法检测筛选出的药物对骨肉瘤细胞凋亡作用,流式细胞仪检测其对细胞周期的影响,小鼠骨肉瘤模型体内实验检测其体内活性。结果齐墩果酸类化合物具有抑制骨肉瘤的作用,齐墩果酸葡萄糖配体衍生物具有诱导骨肉瘤细胞凋亡的作用,并可抑制小鼠骨肉瘤生长,降低肺转移率。结论齐墩果酸葡萄糖配体衍生物具有良好的抗骨肉瘤活性,可为治疗骨肉瘤的新药开发提供参考。

Objective To screen oleanolic acid（3b-hydroxy-olea-12-en-28-oic acid, OA） derivative compound, to verify the inhibitive effect of OA on the activity of ostesarcoma and to find new evidence of a new drug for osteosarcoma. Methods The influence of OA compounds on proliferative activity of osterosarcoma cells was tested by MTT assay. The apoptosis rate was tested by avnnexin V staining. And a mouse model with high metastatic potential was used to investigate the in vivo inhibitive effect of OA drugs. Results Our results demonstrated that the OA compound inhibited the activity of osteosarcoma cells. OA dextrose derivative （Dex-OA） indnced apoptosis of osteosarcoma cells, and inhibited the growth of tumor to decrease potential metastasis to the lungs. Conclusions Dex-OA has potent anti-tumor activity through induction of apoptosis of cancer cells. These findings suggest that Dex-OA or similar compounds might be new drugs for future anti-cancer therapy of osteosarcoma.