Hydroxypropyl-β-cyclodextrin inhibits the development of triple negative breast cancer by enhancing antitumor immunity

Zhu，Mengmeng1; Zhao，Qian1; Zhang，Wenwen2; Xu，Hongmei1; Zhang，Baotong3; Zhang，Shuang1; Duan，Yajun1; Liao，Chenzhong1; Yang，Xiaoxiao1; Chen，Yuanli1

2023-12-01

10.1016/j.intimp.2023.111168

International Immunopharmacology   影响因子和分区

1567-5769

1878-1705

Triple negative breast cancer (TNBC) is regarded as one of the most aggressive forms of breast cancer. Hydroxypropyl-β-cyclodextrin (HP-β-CD) has been used as a therapeutic agent for Niemann-Pick disease Type C (NPC). However, the exact actions and mechanisms of HP-β-CD on TNBC are not fully understood. To examine the influence of HP-β-CD on the proliferation and migration of TNBC cell lines, particularly 4T1 and MDA-MB-231 cells, a range of assays, including MTT, scratch, cell cycle, and clonal formation assays, were performed. Furthermore, the effectiveness of HP-β-CD in the treatment of TNBC was assessed in vivo using a 4T1 tumor-bearing BALB/c mouse model. We demonstrated the anti-proliferation and anti-migration effect of HP-β-CD on TNBC both in vitro and in vivo. High cholesterol diet can attenuate HP-β-CD-inhibited TNBC growth. Mechanistically, HP-β-CD reduced tumor cholesterol levels by increasing ABCA1 and ABCG1-mediated cholesterol reverse transport. HP-β-CD promoted the infiltration of T cells into the tumor microenvironment (TME) and improved exhaustion of CD8 T cells via reducing immunological checkpoint molecules expression. Additionally, HP-β-CD inhibited the recruitment of tumor associated macrophages to the TME via reducing CCL2-p38MAPK-NF-κB axis. HP-β-CD also inhibited the epithelial mesenchymal transition (EMT) of TNBC cells mediated by the TGF-β signaling pathway. In summary, our study suggests that HP-β-CD effectively inhibited the proliferation and metastasis of TNBC, highlighting HP-β-CD may hold promise as a potential antitumor drug.

HP-β-CD Immune microenvironment Metastasis T cells TNBC

SCI

英语

其他

WOS:001109785100001

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85176462711

Scopus

1.Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes,Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions,School of Food and Biological Engineering,Hefei University of Technology,Hefei,China
2.Tianjin Central Hospital of Obstetrics and Gynecology,Tianjin,China
3.Department of Human Cell Biology and Genetics,Southern University of Science and Technology,School of Medicine,Shenzhen,China

Zhu，Mengmeng,Zhao，Qian,Zhang，Wenwen,et al. Hydroxypropyl-β-cyclodextrin inhibits the development of triple negative breast cancer by enhancing antitumor immunity[J]. International Immunopharmacology,2023,125.

Zhu，Mengmeng.,Zhao，Qian.,Zhang，Wenwen.,Xu，Hongmei.,Zhang，Baotong.,...&Chen，Yuanli.(2023).Hydroxypropyl-β-cyclodextrin inhibits the development of triple negative breast cancer by enhancing antitumor immunity.International Immunopharmacology,125.

Zhu，Mengmeng,et al."Hydroxypropyl-β-cyclodextrin inhibits the development of triple negative breast cancer by enhancing antitumor immunity".International Immunopharmacology 125(2023).