洛铂使人类肝癌细胞周期停滞。

Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells.

机构信息

Department of Medical Oncology, Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.

出版信息

J Hematol Oncol. 2010 Oct 31;3:43. doi: 10.1186/1756-8722-3-43.

BACKGROUND

Hepatocellular carcinoma (HCC) still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored.

METHODS

Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR) and protein (Western blot) levels. The phosphorylation status of cyclin-dependent kinases (CDKs) and retinoblastoma (Rb) protein was also examined using Western blot analysis.

RESULTS

Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1), pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27.

CONCLUSION

Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

背景

肝细胞癌（HCC）仍然是中国的一个重大负担。近年来，第三代铂类化合物被提议作为 HCC 的潜在有效药物。然而，需要更多的实验和临床数据来支持这一建议。在本研究中，评估了洛铂在五种 HCC 细胞系中的作用，并从细胞周期动力学的角度探讨了潜在的分子机制。

方法

采用 MTT 细胞增殖实验检测洛铂对人 HCC 细胞系的细胞毒性。用流式细胞术检测细胞周期分布。用 RT-PCR 和 Western blot 检测细胞周期调控基因的表达。还通过 Western blot 分析检测细胞周期蛋白依赖性激酶（CDKs）和视网膜母细胞瘤（Rb）蛋白的磷酸化状态。

结果

洛铂呈剂量依赖性抑制人 HCC 细胞的增殖。对于最敏感的 SMMC-7721 细胞，洛铂可使细胞周期进程在 G1 和 G2/M 期时间依赖性地停滞，这可能与细胞周期蛋白 B、CDK1、CDC25C、磷酸化 CDK1（pCDK1）、pCDK4、Rb、E2F 和 pRb 的下调以及 p53、p21 和 p27 的上调有关。