Apatinib Inhibits Stem Properties and Malignant Biological Behaviors of Breast Cancer Stem Cells by Blocking Wnt/β-catenin Signal Pathway through Downregulating LncRNA ROR

Baohong Jiang; Hongbo Zhu; Liting Tang; Ting Gao; Yu Zhou; Fuqiang Gong; Yeru Tan; Liming Xie; Xiaoping Wu; Yuehua Li

doi:10.2174/1871520621666210412103849

Apatinib Inhibits Stem Properties and Malignant Biological Behaviors of Breast Cancer Stem Cells by Blocking Wnt/β-catenin Signal Pathway through Downregulating LncRNA ROR

Anticancer Agents Med Chem. 2022;22(9):1723-1734. doi: 10.2174/1871520621666210412103849.

Authors

Baohong Jiang¹, Hongbo Zhu², Liting Tang², Ting Gao², Yu Zhou², Fuqiang Gong², Yeru Tan², Liming Xie², Xiaoping Wu², Yuehua Li²

Affiliations

¹ Department of Pharmacy, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan Province, China.
² Department of Medical Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan Province, China.

PMID: 33845750
DOI: 10.2174/1871520621666210412103849

Abstract

Background: Cancer stem cells could influence tumor recurrence and metastasis.

Objective: To develop a new effective treatment modality targeting breast cancer stem cells (BCSCs) and to explore the role of Apatinib in BCSCs.

Methods: BCSCs were isolated from MDA-MB-231 cells by the immune magnetic beads method. BCSCs were treated with Apatinib, lentiviral plasmids (lncRNA ROR), and iCRT-3 (Wnt pathway inhibitors). Viability, colony numbers, sphere numbers, apoptosis, migration, invasion of BCSCs were detected by MTT, colony formation, tumorsphere, flow cytometry, wound-healing, transwell assays, respectively. The expressions of markers (ABCG2, CD44, CD90, and CD24), epithelial-mesenchymal transition (EMT)-related molecules (Ecadherin, N-cadherin, Vimentin, MMP-2, MMP-9), and Wnt/β-catenin pathway-related proteins (Wnt3a, Wnt5a, β-catenin) in breast cancer stem cells were determined by performing Western blot and qRT-PCR analysis.

Results: Apatinib decreased the viability and colony numbers of BCSCs in a concentration-dependent manner, and it also reduced sphere numbers, suppressed migration, invasion and lncRNA ROR expression, and induced apoptosis of BCSCs. However, these results were partially reversed by lncRNA ROR overexpression. Apatinib suppressed stem property, EMT process, and Wnt/β-catenin pathway in BCSCs, which was partially reversed by lncRNA ROR overexpression. Moreover, lncRNA ROR overexpression increased the colony and sphere numbers and promoted the cell viability, apoptosis inhibition, migration, and invasion of BCSCs, but these effects were partially reversed by iCRT-3. LncRNA ROR overexpression increased the stem property, EMT process, and Wnt/β-catenin pathway, which were partially counteracted by iCRT-3.

Conclusion: Apatinib inhibited stem property and malignant biological behaviors of BCSCs by blocking the Wnt/β-catenin signal pathway through down-regulating lncRNA ROR.

Keywords: Apatinib; BCSCs; EMT; LncRNA ROR; Wnt/β-catenin; stem property.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / drug therapy
Breast Neoplasms* / genetics
Breast Neoplasms* / metabolism
Cell Line, Tumor
Cell Movement
Cell Proliferation
Epithelial-Mesenchymal Transition
Female
Humans
Neoplasm Recurrence, Local / pathology
Neoplastic Stem Cells
Pyridines
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / pharmacology
Wnt Signaling Pathway
beta Catenin / metabolism

Substances

Pyridines
RNA, Long Noncoding
beta Catenin
apatinib