瘦素不仅与瘦素受体 (LEPR) 相互作用，还与其他受体相互作用。虽然肾上腺素受体 β2 (ADRB2) 的促癌作用已得到充分证实，但瘦素在三阴性乳腺癌 (TNBC) 中激活 ADRB2 的作用仍不清楚。使用小鼠 TNBC 研究了 LEPR 的促癌作用细胞系、4T1 和 EMT6 以及荷瘤小鼠模型。通过Western blot和qPCR分析TNBC细胞和肿瘤组织中LEPR、NOX4和ADRB2的表达水平。使用流式细胞术和 MitoSox 染色评估活性氧 (ROS) 水平的变化，而免疫荧光双染证实了 LEPR 和 ADRB2 的共定位。 LEPR 激活促进了 NOX4 衍生的 ROS 和线粒体 ROS 的产生，促进 TNBC 细胞增殖和LEPR 抑制剂 Allo-aca 可以减轻迁移的影响。在细胞膜上观察到 LEPR 和 ADRB2 的共表达，生物信息学数据显示两种受体之间呈正相关。瘦素同时激活 LEPR 和 ADRB2，增强细胞内 ROS 的生成并促进肿瘤进展，而特异性 ADRB2 抑制剂 ICI118551 可以有效对抗这一作用。在体内，瘦素注射加速了肿瘤生长和肺转移而不影响食欲，而 Allo-aca 或 ICI118551 治疗减轻了这些影响。这项研究表明，瘦素通过激活 LEPR 和 ADRB2 刺激 TNBC 的生长和转移，从而导致增加活性氧的产生。这些发现强调 LEPR 和 ADRB2 作为 TNBC 的潜在生物标志物和治疗靶点。

Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear.The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NOX4, and ADRB2 in TNBC cells and tumor tissues were analyzed via Western blot and qPCR. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2.LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects.This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.