Background/Objectives: Breast cancer (BC) remains one of the most prevalent and deadly cancers worldwide, with limited access to advanced treatments in developing regions. There is a critical need for novel therapies with unique mechanisms of action, especially to overcome resistance to conventional platinum-based drugs. This study investigates the anticancer potential of the ruthenium complex Bis(quinolin-8-olato)bis(triphenylphosphine)ruthenium(II) (Ru(quin)2) in ER-positive (T47D) and triple-negative (MDA-MB-231) BC cell lines. Results: Ru(quin)2demonstrated dose-dependent cytotoxicity, with IC50 values of 48.3 μM in T47D cells and 45.5 μM in MDA-MB-231 cells. Its cytotoxic effects are primarily driven by apoptosis, as shown by increased BAX expression, enhanced caspase-3 activity, reduced Aurora B kinase levels, and elevated histone release. Ru(quin)2also induced autophagy, evidenced by LC3-I to LC3-II conversion and reduced SQSTM1, partially mediated through MAPK signaling. Furthermore, Ru(quin)2induced G0/G1 cell cycle arrest by downregulating cyclin D1, CDK4, and CDK6, alongside upregulation of the CDK inhibitor p21. Conclusions: Ru(quin)2emerges as a potent candidate for BC treatment, with multiple mechanisms of action involving apoptosis, autophagy, and cell cycle arrest. Further studies are warranted to elucidate its detailed molecular mechanisms and evaluate its therapeutic potential in vivo, moving toward clinical applications for both ER-positive and triple-negative BC management.
背景/目的：乳腺癌仍是全球范围内最常见且致命的癌症之一，在发展中地区获得先进治疗的机会有限。亟需开发具有独特作用机制的新型疗法，特别是用于克服传统铂类药物的耐药性。本研究探讨了钌配合物双(8-羟基喹啉)双(三苯基膦)钌(II)（Ru(quin)2）在雌激素受体阳性（T47D）和三阴性（MDA-MB-231）乳腺癌细胞系中的抗癌潜力。结果：Ru(quin)2表现出剂量依赖性细胞毒性，对T47D细胞的IC50值为48.3 μM，对MDA-MB-231细胞为45.5 μM。其细胞毒性作用主要通过凋亡途径实现，表现为BAX表达增加、caspase-3活性增强、Aurora B激酶水平降低以及组蛋白释放增多。Ru(quin)2还能诱导自噬，表现为LC3-I向LC3-II的转化及SQSTM1减少，该过程部分通过MAPK信号通路介导。此外，Ru(quin)2通过下调细胞周期蛋白D1、CDK4和CDK6，同时上调CDK抑制剂p21，诱导G0/G1期细胞周期阻滞。结论：Ru(quin)2作为乳腺癌治疗的强效候选药物，具有涉及凋亡、自噬和细胞周期阻滞的多重作用机制。需要进一步研究以阐明其详细分子机制，评估其体内治疗潜力，推动其向雌激素受体阳性和三阴性乳腺癌临床治疗应用发展。
肿瘤(癌症)患者之家