Background: The mechanisms underlying the progression and metastasis of triple-negative breast cancer (TNBC) in the context of extended morphine exposure remain poorly understood. Morphine consumption has been a pressing issue in many countries. While the physiological impact of extended morphine use is multifaceted, cancer patients with a history of extended morphine usage often have a poor prognosis.Methods: In this study, we investigated the impact of extended morphine treatment on the transcriptional profiles of TNBC. To this end, mice were administered morphine intraperitoneally for 14 days, followed by the implantation of EO771 cells, which are triple-negative breast cancer cells, into their mammary fat pad. After primary tumors were removed on the 38th day, a subset of mice was continuously given saline or morphine until the 68th day. Tumor size, organ metastasis, and tumor RNA expression were analyzed.Results: Our findings showed that extended exposure to morphine led to an increase in lung metastasis in the mouse model of triple-negative breast cancer. We analyzed RNA sequencing on tumors to compare their transcriptional profiles with or without metastasis. Through pathway analysis, we specifically examined the novel impact of morphine on the downregulation of taurine/hypotaurine biosynthesis. Given that morphine, droperidol (a dopamine receptor antagonist), and naloxone (an opioid receptor antagonist) might act through either opioid receptors or dopamine receptors, we further demonstrated that taurine mitigated EO771 cell invasion induced by morphine but not by droperidol or naloxone treatment. Additionally, morphine treatment markedly decreased the expression ofGAD1, one of the enzymes essential for taurine biosynthesis, whereas droperidol and naloxone did not.Conclusions: The findings of morphine-induced reduction inGAD1levels and the inhibition of invasion by taurine treatment suggest that taurine could serve as a potential supplement for triple-negative breast cancer patients who require morphine as part of their treatment regimen or due to their circumstances.
背景：在长期吗啡暴露背景下，三阴性乳腺癌（TNBC）进展和转移的机制仍不清楚。吗啡使用在许多国家已成为紧迫问题。尽管长期使用吗啡的生理影响是多方面的，但具有长期吗啡使用史的癌症患者往往预后不良。 方法：本研究探讨了长期吗啡处理对三阴性乳腺癌转录谱的影响。为此，我们向小鼠腹腔注射吗啡14天，随后将三阴性乳腺癌细胞EO771植入其乳腺脂肪垫。在第38天切除原发肿瘤后，部分小鼠持续给予生理盐水或吗啡直至第68天。我们分析了肿瘤大小、器官转移情况及肿瘤RNA表达。 结果：研究结果显示，长期吗啡暴露导致三阴性乳腺癌小鼠模型的肺转移增加。通过肿瘤RNA测序分析，我们比较了有无转移情况下的转录谱差异。通过通路分析，我们重点研究了吗啡对牛磺酸/亚牛磺酸生物合成下调的新影响。鉴于吗啡、氟哌利多（多巴胺受体拮抗剂）和纳洛酮（阿片受体拮抗剂）可能通过阿片受体或多巴胺受体发挥作用，我们进一步证明牛磺酸能减轻吗啡诱导的EO771细胞侵袭，但对氟哌利多或纳洛酮处理无此作用。此外，吗啡处理显著降低了牛磺酸生物合成关键酶之一GAD1的表达，而氟哌利多和纳洛酮则无此效应。 结论：吗啡诱导GAD1水平降低以及牛磺酸处理抑制侵袭的发现表明，对于因治疗方案或特殊情况需要使用吗啡的三阴性乳腺癌患者，牛磺酸可能成为一种潜在的补充剂。
肿瘤(癌症)患者之家