P

Jin-hui Yuan, R. Zhang, R. Zhang, Li-Xia Guo, Xing-wang Wang, Dan Luo, Yong Xie, H. Xie
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摘要

目的探讨紫杉醇对人肝癌SMMC-7721的影响及其机制。方法采用台盼蓝排斥法测定体外细胞生长情况。采用SMMC-7721细胞皮下接种Balb/c(nu/nu)裸鼠,建立实验性肝癌模型。用游标卡尺测量肿瘤直径,测定体内肿瘤生长情况。分别用3h -胸腺嘧啶、3h -尿嘧啶和3h -亮氨酸掺入,分析DNA、RNA和蛋白质的合成。利用光镜和电镜观察细胞有丝分裂和凋亡的形态学变化。结果紫杉醇对SMMC-7721人肝癌细胞在2.5nmol/L10nmol/ l范围内的生长有抑制作用,细胞有丝分裂阻滞,细胞凋亡。紫杉醇体外处理72h后,细胞内DNA、RNA和蛋白质的合成均明显受到抑制。2.5nmol/L紫杉醇使3h -胸苷的摄取减少到控制值的34%左右(P£1 / 40.05)。将紫杉醇的剂量增加到20nmol /L时,3h -胸腺嘧啶掺入量下降到控制值的60% (P < 1 / 40.01)。在浓度为20nmol/L时,3h -尿苷和3h -亮氨酸的摄取分别减少到52% (P£1⁄40.05)和63% (P£1⁄40.01)。在体内,紫杉醇10mg/kg,每日1次,连续10d显著抑制SMMC-7721肿瘤生长。第11天观察到肿瘤体积缩小90%以上(P < 1 / 40.01),与有丝分裂阻滞和细胞凋亡相似。结论紫杉醇对人肝癌SMMC-7721具有明显的体外和裸鼠抗肿瘤活性。其机制可能与有丝分裂阻滞以及随后的肝癌细胞凋亡有关。紫杉醇体内给药未见明显毒性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
P
AIM To investigate the effects of taxol on SMMC-7721 human hepatoma and its mechanisms. METHODS In vitro cell growth was assessed by trypan blue exclusion method. Experimental hepatoma model was established by seeding SMMC-7721 cells subcutaneously into Balb/c(nu/nu) nude mice. In vivo tumor growth was determined by measurement of tumor diameter with Vernier calipers. The syntheses of DNA, RNA and protein were analyzed by incorporation of 3H-thymidine, 3H-uridine and 3H-leucine respectively. Using light and electron microscopes to observe the morphological changes of cells including mitosis and apoptosis. RESULTS Taxol was effective against SMMC-7721 human hepatoma cell growth in the ranges of 2.5nmol/L10nmol/Lwith mitotic arrest and apoptosis in vitro. DNA, RNA and protein syntheses in cells were also obviously suppressed by in vitro treatment of taxol for 72h. Taxol at 2.5nmol/L reduced 3H-thymidine uptake to about 34% of the control value (P£1⁄40.05). Increasing the dose of taxol to 20nmol /L resulted in a greater decrease in 3H-thymidine incorporation to 60% of the control value (P£1⁄40.01). At a concentration of 20nmol/L, the 3H-uridine and 3H-leucine uptakes were reduced to 52% (P£1⁄40.05) and 63% (P£1⁄40.01), respectively. In vivo, taxol significantly inhibited SMMC-7721 tumor growth at 10mg/kg, i.p. once daily for 10d. A more than 90% decrease in tumor volume was observed by day 11 (P£1⁄40.01) similarly with mitotic arrest and cell apoptosis. CONCLUSION Taxol has a marked anticancer activity in SMMC-7721 human hepatoma both in vitro and in nude mice. Its mechanisms might be associated with mitotic arrest, subsequently, apoptosis of the hepatoma cells. No obvious toxicity was observed with in vivo administration of taxol.
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