Chen Gong, Zeng Si, Wang Bin, Wang Daguo, Ding Jie, Feng Tao
Department of Anesthesiology, Baoan Central Hospital of Shenzhen, Shenzhen, Guangdong Province, China.
Department of Anesthesiology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Electronic Science and Technology University, Chengdu, China.
Curr Mol Med. 2025;25(4):460-471. doi: 10.2174/0115665240314564241129044548.
Morphine, a mu-opioid receptor (MOR) agonist commonly utilized in clinical settings alongside chemotherapy to manage chronic pain in cancer patients, has exhibited contradictory effects on cancer, displaying specificity toward certain cancer types and doses.
The aim of this study was to conduct a systematic assessment and comparison of the impacts of morphine on three distinct cancer models in a preclinical setting.
Viability and apoptosis assays were conducted on a panel of cancer cell lines following treatment with morphine, chemotherapy drugs alone, or their combination. Oxidative stress levels, along with the activities of superoxide dismutase and catalase, were measured. Rescue studies were also carried out using antioxidant reagents.
Morphine induces resistance to conventional chemotherapeutic agents. It was observed that while morphine affected cell viability differently among ovarian cancer, anaplastic thyroid cancer, and oral squamous cell carcinoma, at concentrations that did not directly impact cancer cell viability, it significantly mitigated the inhibitory effects of chemotherapeutic agents across all tested cancer cells. This phenomenon persisted irrespective of the chemotherapeutic agent used, including cisplatin, doxorubicin, and 5-FU. It remained unaffected by adding naloxone, the MOR receptor antagonist, indicating that morphine's mechanism is independent of the μ- opioid receptor. Moreover, it was demonstrated that morphine heightened cellular reactive oxygen species (ROS) levels and suppressed the activities of superoxide dismutase and catalase. Rescue studies revealed that the addition of antioxidant reversed the protective impact of morphine on cancer cells against chemotherapy.
These findings hold promise in potentially guiding the clinical application of morphine for cancer patients undergoing chemotherapy.
吗啡是一种μ阿片受体（MOR）激动剂，在临床环境中常与化疗联合使用，以管理癌症患者的慢性疼痛，它对癌症表现出矛盾的影响，对某些癌症类型和剂量具有特异性。
本研究的目的是在临床前环境中对吗啡对三种不同癌症模型的影响进行系统评估和比较。
在用吗啡、单独的化疗药物或它们的组合处理后，对一组癌细胞系进行活力和凋亡测定。测量氧化应激水平以及超氧化物歧化酶和过氧化氢酶的活性。还使用抗氧化剂试剂进行了挽救研究。
吗啡诱导对传统化疗药物的耐药性。观察到，虽然吗啡对卵巢癌、间变性甲状腺癌和口腔鳞状细胞癌的细胞活力影响不同，但在不直接影响癌细胞活力的浓度下，它显著减轻了所有测试癌细胞中化疗药物的抑制作用。无论使用何种化疗药物，包括顺铂、阿霉素和5-氟尿嘧啶，这种现象都持续存在。添加MOR受体拮抗剂纳洛酮对其没有影响，表明吗啡的作用机制独立于μ阿片受体。此外，已证明吗啡会提高细胞活性氧（ROS）水平，并抑制超氧化物歧化酶和过氧化氢酶的活性。挽救研究表明，添加抗氧化剂可逆转吗啡对癌细胞抵抗化疗的保护作用。
这些发现有望为正在接受化疗的癌症患者指导吗啡的临床应用。
