PUBLICATION

Aiduqing formula suppresses breast cancer metastasis via inhibiting CXCL1-mediated autophagy

Authors
Yang, B., Peng, F., Zhang, Y., Wang, X., Wang, S., Zheng, Y., Zhang, J., Zeng, Y., Wang, N., Peng, C., Wang, Z.
ID
ZDB-PUB-210713-8
Date
2021
Source
Phytomedicine : international journal of phytotherapy and phytopharmacology   90: 153628 (Journal)
Registered Authors
Keywords
Aiduqing formula, Autophagy, Breast cancer, CXCL1, Metastasis
MeSH Terms
  • Animals
  • Apoptosis
  • Autophagy/drug effects*
  • Breast Neoplasms*/drug therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Chemokine CXCL1/metabolism*
  • Drugs, Chinese Herbal/pharmacology*
  • Female
  • Humans
  • Mice
  • Neoplasm Metastasis/prevention & control*
  • Xenograft Model Antitumor Assays
  • Zebrafish
PubMed
34247114 Full text @ Phytomedicine
Abstract
Metastasis is the most common lethal cause of breast cancer-related death. Recent studies have implied that autophagy is closely implicated in cancer metastasis. Therefore, it is of great significance to explore autophagy-related molecular targets involved in breast cancer metastasis and to develop therapeutic drugs.
This study was designed to investigate the anti-metastatic effects and autophagy regulatory mechanisms of Aiduqing (ADQ) formula on breast cancer.
Multiple cellular and molecular experiments were conducted to investigate the inhibitory effects of ADQ formula on autophagy and metastasis of breast cancer cells in vitro. Meanwhile, autophagic activator/inhibitor as well as CXCL1 overexpression or interference plasmids were used to investigate the underlying mechanisms of ADQ formula in modulating autophagy-mediated metastasis. Furthermore, the zebrafish xenotransplantation model and mouse xenografts were applied to validate the inhibitory effect of ADQ formula on autophagy-mediated metastasis in breast cancer in vivo.
ADQ formula significantly inhibited the proliferation, migration, invasion and autophagy but induced apoptosis of high-metastatic breast cancer cells in vitro. Similar results were also observed in starvation-induced breast cancer cells which exhibited elevated metastatic ability and autophagy activity. Mechanism investigations further approved that either CXCL1 overexpression or autophagic activator rapamycin can significantly abrogated the anti-metastatic effects of ADQ formula, suggesting that CXCL1-mediated autophagy may be the crucial pathway of ADQ formula in suppressing breast cancer metastasis. More importantly, ADQ formula suppressed breast cancer growth, autophagy, and metastasis in both the zebrafish xenotransplantation model and the mouse xenografts.
Our study not only revealed the novel function of CXCL1 in mediating autophagy-mediated metastasis but also suggested ADQ formula as a candidate drug for the treatment of metastatic breast cancer.
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