[4-(2-氯-4a,10a-二氢吩噻嗪-10-基)-丁基]-三苯基-磷鎓抑制骨肉瘤细胞的机制研究

[4-(2-Chloro-4a,10a-Dihydrophenothiazin-10-yl)-Butyl]-Triphenyl-Phosphonium Inhibits Osteosarcoma Cells by Inducing Apoptosis

目的把2-氯吩噻嗪与阳离子基团三苯基膦(TPP)进行化学结构改造,合成新的化合物后检测其抗骨肉瘤活性。方法通过吩噻嗪骨架结构与阳离子线粒体靶向基团相接后用MTT实验、平板克隆形成实验、Transwell迁移和侵袭实验、凋亡和自噬实验检测其抗骨肉瘤活性。结果我们成功合成一种新的吩噻嗪衍生物—[4-(2-氯-4a,10a-二氢吩噻嗪-10-基)-丁基]-三苯基-磷鎓,纯度达98%,实验结果显示该衍生物可抑制骨肉瘤细胞U2OS的增殖、克隆形成、迁移和侵袭能力,呈浓度依赖性。该抑制作用通过诱导凋亡、而不是诱导自噬而实现。结论我们合成的吩噻嗪衍生物具有通过诱导细胞凋亡来抑制骨肉瘤U2OS细胞的作用。

Objective To modify the chemical structure of 2-chlorophenothiazine and cationic group triphenylphosphine(TPP),then test its anti-osteosarcoma activity after synthesizing new compounds.Methods Synthesis of new compound by using 2-chlorophenothiazine and cationic mitochondrial targeting group TPP.The anti-osteosarcoma activity was detected by using MTT test,plate clone formation test,Transwell migration and invasion,apoptosis and autophagy assay.Results We successfully synthesized a new phenothiazine derivative-[4-(2-chloro-4 a,10 a-dihydrophenothiazine-10-yl)-butyl]-triphenyl-phosphonium.The purity was 98%.Experiments showed that the derivative could inhibit the proliferation,clone formation,migration and invasion of osteosarcoma cells U2 OS in a concentration-dependent manner.This inhibitory effect is achieved by inducing apoptosis rather than autophagy.Conclusion Our synthetic phenothiazine derivatives have the effect of inhibiting osteosarcoma U2 OS cells by inducing apoptosis.