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

Int Immunopharmacol. 2023 Nov 6;125(Pt A):111168. doi: 10.1016/j.intimp.2023.111168. Online ahead of print.ABSTRACTTriple 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 media...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Source Type: research