紫杉烷类衍生物Lx2-32c对人卵巢癌A2780细胞的抑制作用

Inhibiting effect of Lx2-32c,one taxane derivant,on the proliferation of human ovary A2780 cells

目的:研究新型紫杉烷类衍生物Lx2-32c体内外对人卵巢癌A2780细胞的生长抑制作用并探讨其机制。方法:体外实验采用培养的人卵巢癌A2780细胞株,利用集落形成法测定Lx2-32c对A2780细胞克隆原细胞的影响,流式细胞术(FCM)测定细胞周期的变化,间接免疫荧光方法观察细胞内微管动力学的改变。体内实验采用人癌细胞裸鼠移植瘤模型观察Lx2-32c对卵巢癌的生长抑制作用。结果:Lx2-32c能够显著抑制A2780细胞的克隆原形成,IC50值为0.13nmol·L-1;Lx2-32c诱导A2780细胞出现G2/M期阻滞;影响细胞内微管的动力学功能,抑制微管解聚,形成稳定的微管束。体内抗肿瘤实验中,Lx2-32c显示出较强的抗肿瘤活性。结论:新型紫杉烷类衍生物Lx2-32c具有较强的细胞毒性和抗肿瘤作用。

Objective： To study the effect of Lx2-32c, one taxane derivant, on the proliferation of human ovary A2780 cells and its mechanism of action. Methods： Cytotoxic effect of Lx2-32c on A2780 cells was tested by clonogenic assay. Cell cycle was determined by flow cytometry （FCM） , and microtubule changes of the cells were visualized by indirect immunofluorescent microscopy. In vivo antitumor activity was tested in nude mice with xenograft of the cancer cells. Results： Lx2-32c significantly inhibited the colony formation of A2780 cells; the ICs0 was 0.13 nmol·L^-1. The FCM analysis showed that Lx2-32c treatment for 24 h arrested A2780 cells in G2/M phase in a concentration-dependent manner. It also formed microtubule bundles, and displayed a robust antitumor activity in nude mice with A2780 cell xenografi. Conclusion： Lx2-32c has the potent cytotoxic and antitumor activity.