嗎啡目前被廣泛使用在許多慢性疼痛治療，對嗎啡慢性使用而有耐受性的病患在得到三陰性乳癌後會繼續使用嗎啡進一步治療癌症疼痛，但慢性嗎啡對三陰性乳癌的影響機制目前並不確定。在本研究中，我們在實驗小鼠連續14天進行腹腔注射嗎啡，以模擬臨床上長期使用嗎啡控制疼痛的情形，以此動物模型進行研究。接著在小鼠體內植入EO771細胞，這是一種來自小鼠、具快速生長特性的三陰性乳癌細胞株。從這些動物模型中採集的腫瘤組織進行基因表現分析，主成分分析與階層式分群分析顯示，根據腫瘤特性呈現出明顯不同的轉錄表現圖譜，清楚顯示出嗎啡誘導的轉移趨勢。
與控制組中未轉移的腫瘤相比，嗎啡誘導的轉移性腫瘤中有較高比例的基因呈現下調表現。功能性富集分析顯示，牛磺酸合成、花生四烯酸代謝、以及腎素-血管張力素系統等途徑有明顯下調。在這些腫瘤中，負責牛磺酸合成的關鍵酵素穀氨酸脫羧酶表現顯著降低。
與動物實驗結果一致，體外實驗中嗎啡處理也增加了癌細胞的侵襲能力，而補充牛磺酸則能有效逆轉這一現象。此外，嗎啡處理會抑制穀氨酸脫羧酶表現，而牛磺酸補充則可恢復其表現水平。
我們的研究結果顯示，嗎啡可能透過下調穀氨酸脫羧酶表現、降低牛磺酸濃度，進而促進三陰性乳癌的轉移。因此，牛磺酸補充可能對於需要長期使用嗎啡的三陰性乳癌患者具有潛在的治療效益。

Morphine is widely used for managing various chronic pain conditions. However, individuals with a history of long-term morphine use may have an increased risk of cancer development or progression due to morphine’s immunomodulatory effects. To investigate the effect of prolonged morphine exposure on the progression of triple-negative breast cancer (TNBC), an animal model was established by intraperitoneally injecting morphine daily for 14 days, simulating chronic clinical use. Subsequently, EO771 cells—rapidly proliferating, mouse-derived TNBC cells—were implanted into these mice. Tumor tissues harvested from the mouse model were subjected to gene expression profiling. Principal component analysis and hierarchical clustering revealed distinct transcriptional signatures linked to tumor characteristics, highlighting a clear morphine-induced metastatic trend. The proportion of downregulated genes was higher in morphine-induced metastatic tumors than in nonmetastatic control tumors. Functional enrichment analyses revealed downregulation of pathways associated with taurine biosynthesis, arachidonic acid metabolism, and the renin-angiotensin system. Glutamate decarboxylase 1 (GAD1), a key enzyme involved in taurine biosynthesis, was markedly suppressed in morphine-induced metastatic tumors. Invasion assays confirmed that morphine enhanced cancer cell invasiveness and that taurine supplementation effectively blocked this effect. Thus, morphine suppressed GAD1 expression in vitro, whereas taurine restored its expression levels. These findings suggest that morphine promotes TNBC metastasis by downregulating GAD1 and suppressing taurine biosynthesis. Furthermore, taurine supplementation may benefit patients with TNBC receiving long-term morphine therapy.