Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114, Taiwan.
Division of Obstetrics and Gynecology, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei City 105, Taiwan.
Int J Mol Sci. 2022 Dec 21;24(1):99. doi: 10.3390/ijms24010099.
Tramadol is a common anesthetic used to treat cancer pain, including endometrial cancer, but its function in endometrial cancer remains unclear. The purpose of this study was to elucidate the antitumor effects of tramadol on human endometrial cancer cells. Colony formation, BrdU, cell cycle profiles, apoptosis, ROS, and Western blot analyses were used to study the response of endometrial cancer cells to tramadol. JC-1 and seahorse metabolic flux assays were used to detect the effect of tramadol on mitochondria in endometrial cancer cells. Combination index was used to detect the interaction of tramadol with chemotherapy drugs in endometrial cancer cells. In this study, we found that tramadol was able to inhibit proliferation and induce cell cycle arrest, ROS generation, and apoptosis in two types of endometrial cancer cells. In addition, tramadol treatment also induced mitochondrial dysfunction in endometrial cancer cells by causing a loss of mitochondrial membrane potential and a decreased oxygen consumption rate. More importantly, the synergetic effect of tramadol with doxorubicin or cisplatin was further confirmed in endometrial cancer cells by the results of the combination index and apoptosis assay. In summary, our findings indicate that tramadol has an antitumor effect on endometrial cancer cells, which might serve as a potential adjuvant therapy strategy for endometrial cancer.
曲马多是一种常用的麻醉剂，用于治疗癌症疼痛，包括子宫内膜癌，但它在子宫内膜癌中的作用尚不清楚。本研究旨在阐明曲马多对人子宫内膜癌细胞的抗肿瘤作用。通过集落形成、BrdU、细胞周期谱、细胞凋亡、ROS 和 Western blot 分析研究了子宫内膜癌细胞对曲马多的反应。使用 JC-1 和 Seahorse 代谢通量分析来检测曲马多对子宫内膜癌细胞中线粒体的影响。使用组合指数来检测曲马多与子宫内膜癌细胞中化疗药物的相互作用。在这项研究中，我们发现曲马多能够抑制两种类型的子宫内膜癌细胞的增殖并诱导细胞周期停滞、ROS 生成和细胞凋亡。此外，曲马多治疗还通过引起线粒体膜电位丧失和耗氧量降低导致线粒体功能障碍。更重要的是，通过组合指数和凋亡分析进一步证实了曲马多与阿霉素或顺铂在子宫内膜癌细胞中的协同作用。总之，我们的研究结果表明，曲马多对子宫内膜癌细胞具有抗肿瘤作用，可能成为子宫内膜癌的一种潜在辅助治疗策略。
