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Synergistic anticancer effect of brusatol combined with paclitaxel on HCT116 cells with preliminary evidence implicating the hsa-miR-29c-3p/CDC42/p53 axis

Year: 2026

Type: article

Abstract: Colorectal cancer (CRC) is a common and life-threatening malignant tumor with a high mortality rate. Paclitaxel is a commonly used chemotherapy drug. Brusatol, a primary chemical component isolated from Brucea javanica , has been reported to significantly inhibit the proliferation of various cancer cell lines. Network pharmacology was employed to predict the core targets and signaling pathways of brusatol against colorectal cancer. This study aims to explore how brusatol combined with paclitaxel might work together to enhance the anticancer effect on HCT116 cells and to evaluate its potential molecular mechanism. The CCK8 and MTT methods were used to assess the growth inhibition effects of paclitaxel, brusatol, and their combination on HCT116 cells. Cell apoptosis and cell cycle distribution were measured using flow cytometry. The levels of apoptosis- and cell cycle-related mRNAs, miRNAs, and proteins were measured by RT-qPCR and Western blot, respectively. The results indicated that, compared to treatment with a single drug, the combined treatment of brusatol and paclitaxel significantly inhibited cell proliferation, increased cell apoptosis, and induced G2/M phase cell cycle arrest in the HCT116 cells. Furthermore, the combined treatment significantly increased the expression of hsa-miR-29c-3p, elevated p53 protein expression, and reduced CDC42 protein expression. These results provide correlative evidence for an association between the synergistic anticancer effect and the hsa-miR-29c-3p/CDC42/p53 signaling axis in HCT116 cells. However, the causal role of this pathway and its dependence on p53 status have not been experimentally established, and further validation in additional cell lines and rescue experiments is warranted.

Source: Scientific Reports

DOI: 10.1038/s41598-026-67929-5

Authors: Zixuan Hu, Caifu Fang, Jiaying Wu, Wei Ren, Dane Huang, Nan Yao