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紫杉醇和吡柔比星诱导人骨肉瘤细胞凋亡的分子机制。

Molecular mechanism of cell apoptosis by paclitaxel and pirarubicin in a human osteosarcoma cell line.

机构信息

Department of Orthopedic Oncology, Third Hospital, Hebei Medical University, Shijiazhuang, PR China. LiusiYuan2004 @ yahoo.com

出版信息

Chemotherapy. 2010;56(2):101-7. doi: 10.1159/000305257. Epub 2010 Mar 30.

DOI:10.1159/000305257
PMID:20357441
Abstract

BACKGROUND

Paclitaxel and pirarubicin exhibit cytotoxic and antitumor activities. However, little is known about the apoptosis-inducing effects of paclitaxel and pirarubicin on human osteosarcoma MG-63 cells.

METHODS

The effects of paclitaxel and pirarubicin on cell cycle arrest and apoptosis were studied in MG-63 cells using flow cytometry. PCNA, Bcl-2, Bax, cyclin D1 and cyclin E expression was assessed by Western blotting.

RESULTS

Paclitaxel and pirarubicin caused G2/M and G0/G1 cell cycle arrest in MG-63 cells, respectively. Apoptosis of MG-63 cells mediated by paclitaxel was dependent on treatment duration. Interestingly, in cells treated with pirarubicin, apoptosis was related to treatment duration at concentrations of 10(2)-10(3) nM, whereas the effect of treatment duration was less marked at concentrations >10(4)-10(5) nM. Furthermore, paclitaxel and pirarubicin suppressed the expression of PCNA, cyclin D1, cyclin E and Bcl-2, and increased Bax expression.

CONCLUSION

These results suggest that the G2/M or G0/G1 cell cycle arrest and apoptosis induced by paclitaxel and pirarubicin are Bcl-2/Bax dependent, suggesting favorable effects of combination therapy with paclitaxel and pirarubicin in the treatment of osteosarcoma.

摘要

背景

紫杉醇和吡柔比星具有细胞毒性和抗肿瘤活性。然而,关于紫杉醇和吡柔比星对人骨肉瘤 MG-63 细胞的凋亡诱导作用知之甚少。

方法

采用流式细胞术研究紫杉醇和吡柔比星对 MG-63 细胞周期阻滞和凋亡的影响。通过 Western blot 检测 PCNA、Bcl-2、Bax、cyclin D1 和 cyclin E 的表达。

结果

紫杉醇和吡柔比星分别导致 MG-63 细胞 G2/M 和 G0/G1 细胞周期阻滞。紫杉醇诱导的 MG-63 细胞凋亡依赖于处理时间。有趣的是,在浓度为 10(2)-10(3) nM 的吡柔比星处理的细胞中,凋亡与处理时间有关,而在浓度 >10(4)-10(5) nM 时,处理时间的影响不太明显。此外,紫杉醇和吡柔比星抑制了 PCNA、cyclin D1、cyclin E 和 Bcl-2 的表达,增加了 Bax 的表达。

结论

这些结果表明,紫杉醇和吡柔比星诱导的 G2/M 或 G0/G1 细胞周期阻滞和凋亡依赖于 Bcl-2/Bax,提示紫杉醇和吡柔比星联合治疗骨肉瘤可能具有良好的效果。

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