Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei Province, China.
Pharmacol Res Perspect. 2022 Oct;10(5):e01016. doi: 10.1002/prp2.1016.
Morphine is frequently applied in cancer patients for pain management. However, its effects on cancer are not well understood but observed to be specific to certain cancer types. We previously revealed the stimulatory properties of morphine in esophageal carcinoma. This work addressed the effects of morphine and its underlying mechanisms in cervical cancer. Proliferation, apoptosis, and migration assays were performed to examine the effects of morphine alone and its combinatory effects with chemotherapeutic drugs. Immunoblotting and biochemical analysis were performed to determine the underlying mechanisms of morphine's action. Morphine promoted proliferation in opioid receptor-dependent manner and stimulated migration in opioid receptor-independent manner. However, morphine did not affect cervical cancer cell survival. Morphine also interfered with all tested chemotherapeutic drugs (e.g., cisplatin, 5-FU, and paclitaxel) and alleviates their efficacy. Mechanistically, morphine-stimulated growth via activating EGFR-mediated signaling pathways and is opioid-receptor-dependent; morphine-stimulated migration via activating RhoA-mediated signaling pathways and this is opioid receptor-independent. Our work suggests a strong correlation of this opioid receptor on growth factor signaling to stimulate growth and opioid receptor-independent activation of RhoA and consequent migration. Our findings have the potential to guide the clinical use of morphine for patients with cervical cancer.
吗啡常用于癌症患者的疼痛管理。然而，其对癌症的影响尚不清楚，但观察到吗啡对某些癌症类型具有特异性。我们之前揭示了吗啡在食管癌中的刺激作用。这项工作研究了吗啡及其在宫颈癌中的潜在机制。进行了增殖、凋亡和迁移实验，以研究吗啡单独作用及其与化疗药物联合作用的效果。免疫印迹和生化分析用于确定吗啡作用的潜在机制。吗啡以阿片受体依赖的方式促进增殖，并以阿片受体非依赖的方式刺激迁移。然而，吗啡并不影响宫颈癌细胞的存活。吗啡还干扰了所有测试的化疗药物（如顺铂、5-FU 和紫杉醇），并降低了它们的疗效。在机制上，吗啡通过激活 EGFR 介导的信号通路刺激生长，且这种作用依赖于阿片受体；吗啡通过激活 RhoA 介导的信号通路刺激迁移，且这种作用不依赖于阿片受体。我们的研究结果表明，阿片受体与生长因子信号之间的强烈相关性可刺激生长，并且阿片受体非依赖性激活 RhoA 及其随后的迁移。我们的研究结果有可能指导吗啡在宫颈癌患者中的临床应用。
