Gong Chen, Si Zeng, Bin Wang, Daguo Wang, Jie Ding, Tao Feng
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引用次数: 0
Abstract
Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: These findings hold promise in potentially guiding the clinical application of morphine for cancer patients undergoing chemotherapy.
期刊介绍：
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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