The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR 999077, P.R. China.
Int J Mol Med. 2018 Mar;41(3):1447-1454. doi: 10.3892/ijmm.2018.3372. Epub 2018 Jan 9.
Colorectal cancer (CRC) is a common and life‑threatening type of malignant cancer, which is associated with a high mortality rate. Cisplatin (CDDP) is a commonly used chemotherapy drug with significant side effects. Brusatol (BR) is one of the principal chemical compounds isolated from the Chinese herb Bruceae Fructus, which has been reported to markedly inhibit the proliferation of numerous cancer cell lines. The present study aimed to investigate the possible synergistic anticancer effects of CDDP combined with BR on CT‑26 cells, and to evaluate the underlying mechanisms of action. The growth inhibitory effects of BR, CDDP, and BR and CDDP cotreatment on CT‑26 cells were assessed by MTT assay. Cell apoptosis were determined by flow cytometry and western blot analysis. The results indicated that compared with single‑agent treatment, cotreatment of CT‑26 cells with CDDP and BR synergistically inhibited cell proliferation and increased cellular apoptosis. Furthermore, treatment of CT‑26 cells with CDDP and BR resulted in a marked increase in the release of cytosolic cytochrome c, decreased expression of procaspase‑3 and procaspase‑9, and upregulation of the B‑cell lymphoma 2 (Bcl‑2)‑associated X protein/Bcl‑2 ratio compared with treatment with BR or CDDP alone. These results strongly suggested that the combination of CDDP and BR was able to produce a synergistic antitumor effect in CRC cells, thus providing a solid foundation for further development of this combination regimen into an effective therapeutic method for CRC.
结直肠癌（CRC）是一种常见且危及生命的恶性肿瘤，其死亡率较高。顺铂（CDDP）是一种常用的化疗药物，具有显著的副作用。鸦胆子苦醇（BR）是从中国草药鸦胆子中分离得到的主要化合物之一，据报道，它能显著抑制多种癌细胞系的增殖。本研究旨在探讨 CDDP 联合 BR 对 CT-26 细胞的可能协同抗癌作用，并评估其作用机制。通过 MTT 法评估 BR、CDDP 及 BR 和 CDDP 联合处理对 CT-26 细胞的生长抑制作用。通过流式细胞术和 Western blot 分析检测细胞凋亡。结果表明，与单药治疗相比，CDDP 和 BR 联合处理 CT-26 细胞可协同抑制细胞增殖并增加细胞凋亡。此外，与单独使用 BR 或 CDDP 相比，用 CDDP 和 BR 处理 CT-26 细胞导致细胞质细胞色素 c 的释放明显增加，procaspase-3 和 procaspase-9 的表达降低，B 细胞淋巴瘤 2（Bcl-2）相关 X 蛋白/Bcl-2 比值上调。这些结果强烈表明，CDDP 和 BR 的联合使用能够在 CRC 细胞中产生协同的抗肿瘤作用，从而为进一步将该联合方案开发为 CRC 的有效治疗方法提供了坚实的基础。
