Anemoside B4 sensitizes human colorectal cancer to fluorouracil-based chemotherapy through src-mediated cell apoptosis

Anemoside B4 通过 src 介导的细胞凋亡增强人类结直肠癌对氟尿嘧啶化疗的敏感性

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作者:Xing He, Jun Tang, He-Zhong Yan, Jiao-Xue Wang, Hai-Qing Li, Xiao-Wei Duan, Sen-Yuan Yu, Xi-Lu Hou, Guo-Bin Liao, Wei Liu

Abstract

Currently, 5-Fluorouracil (5-FU) based chemotherapy is the primary option for colorectal cancer after surgery, whereas chemotherapy resistance related mortality is observed in a large proportion of patients. Anemoside B4 (AB4) is a triterpene saponin, which exhibits a considerable activity in oncotherapy. In this study, we explored the efficacy of AB4 in FU-based chemotherapy in colorectal cancer cells and the underlying molecular mechanisms. Our results indicated a significant synergistic activity of AB4 in 5-FU treated colorectal cancer cells. Furthermore, AB4 treatment eliminated colorectal cancer stem cells by promoting apoptotic cell death in 5-FU resistant colorectal cancer cells. Mechanically, AB4 activated caspase-9 pathway in 5-FU resistant colorectal cancer cells. Elevated Src activity induced cell apoptosis and cancer stem cells elimination effects in AB4 treated colorectal cancer cells. In conclusion, AB4 showed promising sensitization effect in the FU-based chemotherapy of colorectal cancer. Our study may pave a way to ameliorate FU-based chemotherapeutic efficiency in colorectal cancer.

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