Wu Yingchao, Cui Jiaqi, Chen Liushan, Chen Jieting, Huang Junfeng, Yang Congwen, Liang Yuqi, Chen Qianjun, Zuo Qian
Chinese Medicine Guangdong Laboratory, Hengqin, 519031, Guangdong, China.
State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China.
Nat Prod Bioprospect. 2025 Aug 21;15(1):57. doi: 10.1007/s13659-025-00543-6.
Depression promotes breast cancer progression. Given the lack of specific targets for depression-associated breast cancer, there are currently no therapeutic drugs for this type of breast cancer.
Transcriptomic analysis was conducted to identify and functionally annotate genes with differential expression in breast cancer patients exhibiting depressive symptoms. Subsequently, Mendelian randomization was employed to investigate the causal associations between these pivotal genes and breast cancer, thereby validating their potential roles as therapeutic targets. Furthermore, molecular docking techniques were utilized to screen for candidate compounds that may exert therapeutic effects on depression-associated breast cancer. The efficacy of the selected compounds was further assessed using both in vitro cellular experiments and in vivo animal models.
We identified IL-8 as a key gene involved in depression-mediated breast cancer progression using transcriptomics. Mendelian randomized analysis suggested that high IL-8 expression promoted breast cancer progression. Further studies demonstrated that IL-8 mediated the breast cancer-promoting effect of depression through the receptor CXCR2. Evidence from both in vitro and in vivo experiments indicates that senkyunolide H may exert its therapeutic effect by regulating CXCR2, thereby counteracting the protumor effects associated with depression in breast cancer.
Depression activates CXCR2-mediated breast cancer cell proliferation through IL-8, and senkyunolide H regulates CXCR2 and inhibits its ability to block the cancer-promoting effects of depression, ultimately inhibiting the growth of breast cancer in the context of depression.
抑郁症会促进乳腺癌进展。鉴于缺乏与抑郁症相关乳腺癌的特异性靶点，目前尚无针对这类乳腺癌的治疗药物。
进行转录组分析，以鉴定和功能注释在表现出抑郁症状的乳腺癌患者中差异表达的基因。随后，采用孟德尔随机化研究这些关键基因与乳腺癌之间的因果关联，从而验证它们作为治疗靶点的潜在作用。此外，利用分子对接技术筛选可能对抑郁症相关乳腺癌发挥治疗作用的候选化合物。使用体外细胞实验和体内动物模型进一步评估所选化合物的疗效。
我们通过转录组学确定白细胞介素-8（IL-8）是参与抑郁症介导的乳腺癌进展的关键基因。孟德尔随机分析表明，高IL-8表达促进乳腺癌进展。进一步研究表明，IL-8通过受体CXCR2介导抑郁症促进乳腺癌的作用。体外和体内实验证据均表明，川芎内酯H可能通过调节CXCR2发挥其治疗作用，从而抵消与抑郁症相关的乳腺癌促肿瘤作用。
抑郁症通过IL-8激活CXCR2介导的乳腺癌细胞增殖，而川芎内酯H调节CXCR2并抑制其阻断抑郁症促癌作用的能力，最终在抑郁症背景下抑制乳腺癌生长。
