N-钙黏蛋白与Wnt/β-catenin通路在骨髓间充质干细胞与白血病干细胞中的耐药机制研究<sup>*</sup>

doi:10.3969/j.issn.1671-7171.2024.05.013

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Abstract 【Objective】To explore the molecular mechanisms of the N-cadherin and the Wnt/β-catenin pathway facilitate drug resistance in leukemia stem cells (LSC) and mesenchymal stem cells (MSC).【Methods】The study included 65 patients with acute myeloid leukemia (AML), of whom 41 achieved complete remission (CR group) and 24 did not (non-remission, NR group). The expression of N-cadherin in CD34⁺CD38^- stem cells was compared between these two groups. The CD34⁺CD38^- Kg1α cells were further divided into six groups based on different treatments with MSC or idarubicin (IDA) that cell proliferation, apoptosis, and levels of N-cadherin and β-catenin were assessed. The cell adhesion and anti-apoptotic capabilities were also evaluated.【Results】The N-cadherin expression in the NR group compared was significantly higher than that in the CR group (P<0.01).The apoptosis rate in the LSC+IDA group (Group B) was significantly higher than that in the LSC and MSC co-culture + IDA group (Group D) (P<0.05). At IDA concentrations of 100 and 200 nmol/L, the proliferation inhibition rate in Group B was significantly higher than that in Group D (P<0.05). The colony formation rate in Group B was significantly lower than that in Group D (P<0.05). The Western blot results showed that the expression levels of both N-cadherin and β-catenin were higher in direct co-culture condition of MSC than in solo cultures or non-contact co-cultures. In co-culture condition with MSC, LSC showed increased expression levels of N-cadherin and β-catenin, along with an increase in nuclear β-catenin level.【Conclusion】MSCs in the bone marrow microenvironment can support the proliferation of LSC through N-cadherin-mediated adhesion and promote the activation of the Wnt/β-catenin pathway in LSC, thereby enabling them to evade the cytotoxic effects of chemotherapy.

Key words： Leukemia, Myeloid, Acute Calcium-Binding Proteins Drug Resistance, Neoplasm

Received: 27 January 2024

PACS:

R733.72

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http://journal07.magtech.org.cn/yxlcyj/EN/10.3969/j.issn.1671-7171.2024.05.013 OR http://journal07.magtech.org.cn/yxlcyj/EN/Y2024/V41/I5/688

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