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Sanguisorba officinalis L. suppresses 5-fluorouracil-sensitive and-resistant colorectal cancer growth and metastasis via inhibition of the Wnt/β-catenin pathway

Wnt信号通路 下调和上调 转移 癌症研究 结直肠癌 细胞凋亡 连环素 细胞生长 波形蛋白 活力测定 体内 化学 癌症 生物 医学 信号转导 免疫学 内科学 免疫组织化学 生物化学 生物技术 基因
作者
Weijia Zhang,Chang Peng,Jiahui Yan,Pengting Chen,Jiang Cheng,Shuyi Sang,Yuemei Yuan,Yanjun Hong,Meicun Yao
出处
期刊:Phytomedicine [Elsevier]
卷期号:94: 153844-153844 被引量:16
标识
DOI:10.1016/j.phymed.2021.153844
摘要

Colorectal cancer (CRC) is a widespread cancer with high morbidity and mortality. Chemoresistance and metastasis are the current challenges for CRC treatment. Sanguisorba officinalis Linn. (called DiYu in Chinese, DY) is a traditional Chinese medicine (TCM) whose root is long used as medicinal part. In our previous study, the aqueous extract of DY could inhibit the Wnt/β-catenin pathway and showed great antitumor effect against CRC. The Wnt/β-catenin pathway is involved in CRC chemoresistance and metastasis. However, there is little study on the antitumor and antimetastatic effects of DY on resistant CRC cells. The aim of this study is to explore the effect of aqueous extract of DY on the growth and metastasis of 5-fluorouracil (5-FU) sensitive and resistant CRC, and to elucidate the underlying molecular mechanism.In this study, cell viability, cell colony formation and apoptosis analyses were performed to verify the in vitro antitumor effect of DY on 5-FU-sensitive and -resistant CRC cells. Next, transwell assays were used to test the inhibition activity of DY on CRC migration and invasion. Western Blotting assays were carried out to identify the molecular mechanism underlying the efficacy of DY extract. Xenograft CRC nude mice model and tumor metastasis model were used to confirm the in vivo antitumor and antimetastatic effects of DY.DY inhibited cell proliferation and apoptosis via the upregulation of Bax, cleaved-caspase3 and cleaved-PARP proteins and downregulation of Bcl-2 protein. DY also inhibited cell migration and invasion via the downregulation of N-cadherin, vimentin and snail proteins and upregulation of E-cadherin protein, demonstrating that DY suppressed cell metastasis by reversing epithelial-to-mesenchymal transition (EMT) procession. Moreover, the protein expression levels of β-catenin in whole cell, cytoplasm and nucleus were decreased after DY treatment. Taken together, DY suppressed CRC cell growth and metastasis via inhibition of the Wnt pathway. Additionally, DY also demonstrated effective antitumor and anti-metastasis activities in vivo.In conclusion, DY suppressed the growth and metastasis of 5-FU-sensitive and -resistant CRC via inhibition of the Wnt pathway, which indicated that DY could be a potential drug to treat CRC patients and improve clinic outcome.
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