Women with breast cancer (BC) are often combined with psychological disorder such as depression and anxiety. Depression is associated or correlated with increased toxicity and severity of physical symptoms. However, the mechanism of BC progression related to the regulation of emotion-related circuitry remains to be further explored. The study aims to investigate indoleamine 2,3-dioxygenase (IDO) pathway mechanism underlying stress-induced progression of BC. BC cell line 4T1 was subcutaneously inoculated into BALB/c mice, and they then received daily chronic unpredictable mild stressors (CUMS) for 12 weeks. Depression-like behavior tests were conducted, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and novelty suppressed feeding test (NSF). The levels of 5-Hydroxytryptamine (5-HT) and inflammatory factors, IL-6, CXCL1, IL-10 and IL-4 were measured by enzyme linked immunosorbent assay (ELISA) of mouse serum. Immunohistochemical staining was performed to detect Ki67- or FOXP3-positive tumor cells. The status of IDO signaling pathway was assessed by immunoblotting analysis. CUMS induced depression-like behaviors, decreased the level of 5-HT, promoted tumor progression, enhanced the immunohistochemical staining of Ki-67, and promoted the activation of IDO signaling pathway in BC mice. The IDO signaling pathway was disrupted in mice by lentiviral transduction of shRAN-IDO. Lentivirus-mediated IDO knockdown attenuated CUMS-induced depression-like behaviors, increased the level of 5-HT, inhibited tumor progression, and reduced the immunohistochemical staining of Ki-67 in BC mice. The present study suggests that disruption of IDO signaling pathway alleviates CUMS-induced depression-like behaviors and inhibits tumor progression in BC mice.

患有乳腺癌 (BC) 的女性通常伴有抑郁和焦虑等心理障碍。抑郁症与身体症状的毒性增加和严重程度有关或相关。然而，与情绪相关回路调节相关的 BC 进展机制仍有待进一步探索。该研究旨在研究应激诱导的 BC 进展背后的吲哚胺 2,3-双加氧酶 (IDO) 通路机制。将 BC 细胞系 4T1 皮下接种到 BALB/c 小鼠体内，然后它们每天接受慢性不可预知的温和应激源 (CUMS)，持续 12 周。进行了抑郁样行为测试，包括蔗糖偏好测试（SPT）、悬尾测试（TST）、强迫游泳测试（FST）和新奇抑制喂养测试（NSF）。通过小鼠血清的酶联免疫吸附测定 (ELISA) 测量 5-羟色胺 (5-HT) 和炎症因子、IL-6、CXCL1、IL-10 和 IL-4 的水平。进行免疫组织化学染色以检测 Ki67 或 FOXP3 阳性肿瘤细胞。通过免疫印迹分析评估 IDO 信号通路的状态。CUMS诱导BC小鼠抑郁样行为，降低5-HT水平，促进肿瘤进展，增强Ki-67免疫组化染色，促进IDO信号通路激活。通过 shRAN-IDO 的慢病毒转导，IDO 信号通路在小鼠体内被破坏。慢病毒介导的 IDO 敲低减弱了 CUMS 诱导的抑郁样行为，增加了 5-HT 的水平，抑制了肿瘤进展，并减少了 BC 小鼠中 Ki-67 的免疫组织化学染色。