Department of Nursing, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha, 410005, China.
Department of Respiratory Medicine, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Changsha, 410005, China.
Sci Rep. 2024 Nov 8;14(1):27169. doi: 10.1038/s41598-024-73736-7.
Lung carcinoma, predominantly manifested as non-small cell lung cancer (NSCLC), significantly contributes to oncological mortality, underscoring an imperative for novel therapeutic paradigms. Amidst this context, the present investigation delineates the synergistic potentiation of doxorubicin (DOX)-a canonical chemotherapeutic-by Ursodeoxycholic acid (UDCA), a compound with a historical pedigree in hepatobiliary medicine, now repositioned within oncological pharmacotherapy due to its dichotomous cellular modulation-affording cytoprotection to non-malignant epithelia whilst eliciting apoptotic cascades in neoplastic counterparts. This study, through a rigorous methodological framework, elucidates UDCA's capacity to inhibit NSCLC cellular proliferation and induce apoptosis, thereby significantly amplifying DOX's chemotherapeutic efficacy. Notably, the co-administration of UDCA and DOX was observed to attenuate DOX-induced autophagy via the modulation of the TGF-β/MAPK signaling axis, a pathway pivotal in mediating cellular survival and autophagic mechanisms. Such findings not only underscore the therapeutic potential of UDCA as a chemosensitizer but also illuminate the molecular underpinnings of its modulatory effects, thereby contributing to the corpus of knowledge necessary to surmount chemoresistance in NSCLC. The implications of this research are twofold: firstly, it offers a compelling evidence base for the clinical reevaluation of UDCA in combinatory chemotherapeutic regimens; secondly, it posits a novel mechanistic insight into the modulation of chemotherapeutic efficacy and resistance. Collectively, these insights advocate for the expedited clinical translation of UDCA-DOX synergy, potentially heralding a paradigm shift in the management of NSCLC, thereby addressing a critical lacuna in contemporary oncological therapy.
肺癌，主要表现为非小细胞肺癌 (NSCLC)，对肿瘤死亡率有重大影响，因此需要新的治疗模式。在这种情况下，本研究描述了多柔比星 (DOX) - 一种经典的化疗药物 - 与熊去氧胆酸 (UDCA) 的协同增效作用。UDCA 是一种在肝胆医学中有历史渊源的化合物，由于其对细胞的双重调节作用（对非恶性上皮细胞提供细胞保护，而对肿瘤细胞则引发凋亡级联反应），现已重新定位在肿瘤药理学中。本研究通过严格的方法学框架，阐明了 UDCA 抑制 NSCLC 细胞增殖和诱导凋亡的能力，从而显著增强了 DOX 的化疗疗效。值得注意的是，UDCA 和 DOX 的联合给药观察到通过调节 TGF-β/MAPK 信号轴来抑制 DOX 诱导的自噬，该途径在介导细胞存活和自噬机制中起着关键作用。这些发现不仅突出了 UDCA 作为化疗增敏剂的治疗潜力，还阐明了其调节作用的分子基础，从而为克服 NSCLC 化疗耐药性提供了必要的知识基础。这项研究的意义有两个方面：首先，它为 UDCA 在联合化疗方案中的临床重新评估提供了令人信服的证据基础；其次，它提出了一种关于调节化疗疗效和耐药性的新机制见解。总的来说，这些见解主张加速 UDCA-DOX 协同作用的临床转化，可能预示着 NSCLC 管理的范式转变，从而解决当代肿瘤治疗中的一个关键空白。
