Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
J Oncol. 2012;2012:601682. doi: 10.1155/2012/601682. Epub 2012 May 28.
Purpose. To explore the effects of cucurbitacin B on the radiation survival of human breast cancer cells and to elucidate the cellular mechanism of radiosensitization if any. Materials and Methods. Human breast carcinoma cell lines were treated with cucurbitacin B before irradiation with 0-10 Gy of (137)Cs gamma rays. The effect of cucurbitacin B on cell-survival following irradiation was evaluated by colony-forming assay. Cell cycle distributions were investigated using flow cytometry. Real-time PCR and western blots were performed to investigate the expression of cell cycle checkpoints. Results. Cucurbitacin B inhibited breast cancer cell proliferation in a dose-dependent manner. Only MDA-MB-231 and MCF7:5C cells but not SKBR-3 cells were radiosensitized by cucurbitacin B. Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells. Moreover, Real-time PCR and western blot analysis demonstrated upregulated p21 expression before irradiation, a likely cause of the cell cycle arrest. Conclusion. Taken together, these findings suggest that cucurbitacin B causes radiosensitization of some breast cancer cells, and that cucurbitacin B induced G2/M arrest is an important mechanism. Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment.
目的。探讨葫芦素 B 对人乳腺癌细胞辐射存活的影响，并阐明其放射增敏作用的细胞机制（如果有）。
材料和方法。用葫芦素 B 处理人乳腺癌细胞系，然后用 0-10Gy 的（137）Csγ射线照射。用集落形成实验评价照射后葫芦素 B 对细胞存活的影响。用流式细胞术研究细胞周期分布。实时 PCR 和 Western blot 用于研究细胞周期检查点的表达。
结果。葫芦素 B 呈剂量依赖性抑制乳腺癌细胞增殖。只有 MDA-MB-231 和 MCF7:5C 细胞而非 SKBR-3 细胞被葫芦素 B 放射增敏。DNA 含量的流式细胞术分析表明，葫芦素 B 导致 MDA-MB-231 和 MCF7:5C 细胞发生 G2/M 期阻滞，但 SKBR-3 细胞没有。此外，实时 PCR 和 Western blot 分析表明，照射前 p21 表达上调，这可能是细胞周期阻滞的原因。
结论。总之，这些发现表明葫芦素 B 导致一些乳腺癌细胞放射增敏，而葫芦素 B 诱导的 G2/M 期阻滞是一个重要的机制。因此，葫芦素 B 与放射治疗的联合可能适用于实验性乳腺癌治疗。
