Synergistic antitumor effect of brusatol combined with cisplatin on colorectal cancer cells

Chen,Hai‑Ming; Lai,Zheng‑Quan; Liao,Hui‑Jun; Xie,Jian‑Hui; Xian,Yan‑Fang; Chen,Yun‑Long; Ip,Siu‑Po; Lin,Zhi‑Xiu; Su,Zi‑Ren

doi:10.3892/ijmm.2018.3372

Synergistic antitumor effect of brusatol combined with cisplatin on colorectal cancer cells

Authors:
- Hai‑Ming Chen
- Zheng‑Quan Lai
- Hui‑Jun Liao
- Jian‑Hui Xie
- Yan‑Fang Xian
- Yun‑Long Chen
- Siu‑Po Ip
- Zhi‑Xiu Lin
- Zi‑Ren Su
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Affiliations: 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, Department of Clinical Pharmacy and Pharmaceutical Services, Shenzhen Sixth People's Hospital (Nanshan Hospital), Shenzhen 518060, P.R. China, College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
Published online on: January 9, 2018 https://doi.org/10.3892/ijmm.2018.3372
Pages: 1447-1454
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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