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XIAOPI formula promotes breast cancer chemosensitivity via inhibiting CXCL1/HMGB1-mediated autophagy.

Abstract
XIAOPI formula is a national approved drug prescribed to patients with high breast cancer risk. Previously we demonstrated that XIAOPI formula could inhibit breast cancer metastasis via suppressing CXCL1 expression, and postulated that "autophagy in cancer" might be one of its most core anti-cancer mechanisms. However, whether XIAOPI formula could be simultaneously applied with chemodrugs and their synergistic mechanisms are still remained unknown. In the present study, XIAOPI formula at non-cytotoxic doses could synergistically enhance the chemosensitivity of breast cancer cells MDA-MB-231 and MCF-7. We found that rapamycin-induced autophagy could reduce the chemosensitivity of breast cancer cells to XIAOPI formula, and the autophagy suppression and chemosensitizing activity of this formula was CXCL1-dependent. The evidence came from that XIAOPI formula was associated with a lower expression of CXCL1 combined with either rapamycin or taxol alone. Besides, the inhibitory effect of XIAOPI formula on the LC3-II and ABCG2 signals was weakened following CXCL1 over-expression, whereas P62 upregulation induced by XIAOPI formula was re-declined. A high throughput - qPCR (HT-qPCR) assay identified HMGB1 as the main autophagic target of XIAOPI formula in chemosensitizing breast cancer. and furhter validation suggested XIAOPI formula exerted chemosensitivity mainly via CXCL1/HMGB1 autophagic axis. Finally, we generated both mice and zebrafish xenotransplantation models bearing MDA-MB-231 breast cancer cells, and found that XIAOPI formula safely enhanced in vivo taxol chemosensitivity on breast cancer. Taken together, XIAOPI formula is a potential adjuvant drug via inhibiting CXCL1/HMGB1-mediated autophagy for breast cancer treatment with good safety.
AuthorsNeng Wang, Bowen Yang, Gulizeba Muhetaer, Shengqi Wang, Yifeng Zheng, Jiahong Lu, Min Li, Fengxue Zhang, Honglin Situ, Yi Lin, Zhiyu Wang
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 120 Pg. 109519 (Dec 2019) ISSN: 1950-6007 [Electronic] France
PMID31629951 (Publication Type: Journal Article)
CopyrightCopyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Chemokine CXCL1
  • Drugs, Chinese Herbal
  • HMGB1 Protein
  • HMGB1 protein, human
  • Epirubicin
  • Paclitaxel
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, metabolism, pharmacology)
  • Autophagy
  • Breast Neoplasms (drug therapy)
  • Cell Line
  • Cell Survival
  • Chemokine CXCL1 (genetics, metabolism)
  • Drug Resistance, Neoplasm (drug effects)
  • Drug Synergism
  • Drugs, Chinese Herbal (pharmacology)
  • Epirubicin (metabolism)
  • Female
  • Gene Expression Regulation (drug effects)
  • HMGB1 Protein (genetics, metabolism)
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental (drug therapy)
  • Oviposition (drug effects)
  • Paclitaxel (administration & dosage, pharmacology)
  • Zebrafish

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