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通过 src 介导的细胞凋亡，黄花夹竹桃苷 B4 使人类结直肠癌细胞对基于氟尿嘧啶的化疗敏感。

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

机构信息

Department of Gastroenterology, The 901 Hospital of Joint Logistics Support Force, Hefei 230031, Anhui, China.

出版信息

Aging (Albany NY). 2021 Dec 10;13(23):25365-25376. doi: 10.18632/aging.203751.

DOI:10.18632/aging.203751
PMID:34890366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8714157/
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.

摘要

目前，5-氟尿嘧啶（5-FU）为基础的化疗是结直肠癌手术后的主要选择，而相当一部分患者观察到化疗耐药相关的死亡。刺五加皂苷 B4（AB4）是一种三萜皂苷，在肿瘤治疗中表现出相当大的活性。在这项研究中，我们探讨了 AB4 在基于 5-FU 的结直肠癌细胞化疗中的疗效及其潜在的分子机制。我们的结果表明 AB4 在 5-FU 处理的结直肠癌细胞中具有显著的协同活性。此外，AB4 通过促进 5-FU 耐药结直肠癌细胞中的凋亡细胞死亡来消除结直肠癌细胞干细胞。在机制上，AB4 在 5-FU 耐药结直肠癌细胞中激活了半胱天冬酶-9 途径。Src 活性升高诱导 AB4 处理的结直肠癌细胞中的细胞凋亡和癌细胞干细胞消除作用。总之，AB4 在基于 FU 的结直肠癌化疗中显示出有希望的增敏作用。我们的研究可能为改善结直肠癌基于 FU 的化疗效果铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/8a4c03012a7d/aging-13-203751-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/2394fee41ac2/aging-13-203751-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/f9d9cffba0d3/aging-13-203751-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/3b52d3cebd8b/aging-13-203751-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/df6965dd6b0c/aging-13-203751-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/8a4c03012a7d/aging-13-203751-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/2394fee41ac2/aging-13-203751-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/f9d9cffba0d3/aging-13-203751-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/3b52d3cebd8b/aging-13-203751-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/df6965dd6b0c/aging-13-203751-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c029/8714157/8a4c03012a7d/aging-13-203751-g005.jpg

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