鬼臼毒素衍生物OAMDP诱导HeLa细胞凋亡

Apoptosis induced by podophyllotoxin derivative OAMDP in HeLa cells

鬼臼毒素衍生物OAMDP对人宫颈癌HeLa细胞显示了细胞增殖抑制活性,并呈现一定的时间和剂量的依赖性,对其作用机制进行初步研究。Hoechst 33258染色荧光显微镜观察发现OAMDP能诱导HeLa细胞核形态学改变,部分细胞呈现典型的凋亡形态学特征;AnnexinⅤ-FITC/PI荧光双染流式细胞术检测亦证实OAMDP可以诱导HeLa细胞发生凋亡;Rhodamine123染色线粒体膜电位检测发现OAMDP会引起HeLa细胞线粒体膜电位的下降。Western Blot分析显示OAMDP上调HeLa细胞凋亡相关蛋白Bax,下调Bcl-2的表达。此外OAMDP能使HeLa细胞阻滞于S期。总之,OAMDP能够诱导HeLa细胞凋亡和S期阻滞,可能成为一种新型的抗肿瘤药物。

A novel podophyllotoxin derivative, 4/3-（ 1,3, 4-oxadiazole-2-amino-5-methyl） -4-deoxypodophyllotoxin （ OAMDP）, showed the antiproliferative effect, for which OAMDP could suppress the proliferation of HeLa cells in a dose-and time-dependent manner. Furthermore, its molecular mechanism in HeLa cells was investigated. In HeLa ceils treated by OAMDP, topical morphological changes of apoptotic body formation were observed by Hoechst 33258 staining. Cell apoptosis was also confirmed by Annexin V-FITC/PI double staining assay. Rhodamine 123 label testing revealed that the mitochondrial membrane potential （Ag4,n） of ceils was decreased. OAMDP increased apoptotic cell population by induction of bax and reduction of Bcl-2 expression. Moreover, cell cycle analysis showed that OAMDP induced S phase arrest in HeLa cells. Our results indicated that OAMDP, with the ability to cause cell cycle S arrest and apoptosis, has the potential to become a novel antitumor agent.